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The origin and fate of plasmacytes. A comparative histologic study of plasmacytes of normal lymph nodes and tumors of multiple myeloma

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T H E OZZIGIS A S D FATE OE' PLASVACYTES
A COMPARATIVE HISTOLOGIC S T U D Y O F PLA SMA CY TES O F Y O RMA L
L I ' n w H NODES AXD TUMORS OF MULTIPLE MYELOMA
HARVEY E. JORDAN
1)epartnient of Anato?iiy, School of Medicine, Uniuei-sity of Virginia
SIXTEEN FIGURES
The origin of plasmacytes has been variously assigned to
lymphocytes (Dubreuil and Favre, '21 ; Downey, '27 ; Bloom,
'28 ; ;\laximow, '28 ; Jordan, '29 ; Alichels, '35), or connectivetissue cells (Custer, '49 ; Propp, Gorham and Kantor, '49),
or concomitantly to both (Kingsley, '24; Campbell and Good,
'49). I n general, their source in pathological material has
been ascribed to some form of connective-tissue cell (fibroblast, reticulo-endothelial cell, histiocyte, niesoglia cell) ; in
presumably normal lymphoid tissue, to lymphocytes ; in bone
marrow, to lymphocytes, reticulo-endothelium or hemocytoblasts (Downey, '28 ; Lichtenstein, '52). Intermediate stages
in the transformation of the ancestral cells into definitive
plasniacytes have become recognized a s plasmablasts and
proplasmacytes, also designated a s plasrriacytic polyblasts.
The close cytologic similarity among plasmablasts, lymphoblasts and hemocytoblasts poses the question of possible
identity and developmental pluripotentialitp.
MATERIAL AND METTIODS
The material for this investigation included : (1) Suhmaxill a q - lymph nodes of albino rats of ages 15 days, 30 days, and
6 months, fixed in Zenker-formol solution. Sections were
stained either with eosin-azure or hematoxylin and eosin.
F r e s h mounts were studied in chicken plasma under a vaseline-sealed coverglass. The submaxillary lymph nodes were
This inrestigation ims supported by a grant f m m the Landon R. Funsten
Cancer Research Fund.
325
326
HARVEY E. J O R U A S
chosen for this study because of the relatively great abundance
of plasmacytes in the medullary cords. The 15-day material
was kindly supplied by Dr. J. E. Kindred from his collection
of slides used in his investigation of 1940. ( 2 ) Sections of
autopsy material in the Department of Pathology, University
of Virginia, from a case of multiple iiiyelonia in a 68-year-old
woman. The material had been fixed in Zenker-forniol and
sections were stained with hematoxylin and eosin. Conditions
in sections of inarro~vfrom a rib were of special interest.
( 3 ) Sections of biopsy material from a coinpact tumor at the
sternal end of the left clavicle of an elderly female patient
with multiple myeloma. This material was ltiiidlp supplied
by Dr. H. R. Peamall of the Jefferson Hospital, Xoanolte,
Virginia. The tissue had been fixed in Zenlter-forniol and the
sections stained with heiiiatosyliii and eosin. (4) Aspirated
sternal marrow, supplied by Dr. P. H. TYornom, from an
elderly female patient with multiple iiiyelonia in the University Hospital. This patient died two months after the
date of the aspii*ation. Heparin was added to the aspirated
material to prevent coagulation. The study included fresh
mounts, both unstained and stained supravitally with J a m s
green and neutral red : also smears stained with Triglit’s
stain.
Subnatr xiI1( I r y 1!JII1 p h
ii o
(1o.s of
t re u 1b i i i o r cit s
111 (1 21
Typical conditioiis in the medullary cords of submasillary
lymph nodes are illustrated in figures 1 and 12. Figure 1
shows an area of typical plasmacytes. Figure 1 2 is a drawiiig
of a group of selected plasinacytes from a small region of a
medullary cord, illustrating variations in size, shape, nuclear
characteristics, cytoplasmic characteristics, and two stages
in amitotic division. These plasinacytes varied in size from
the smallest with a diameter of approximately 5.5 p to the
largest with a diameter of approximately 9 p. Cells of these
extreme sizes were relatively few in number ; the predominating plasmacytes had a diameter of about 7 p. The prevailing
shape was spherical 01’ oval; where the cells were closely
THE ORIGIN A X D PATE O F I’LASMACYTES
327
packed the origiiial spheroidal shape was modified to polyhedral foriii. BIaiiy of these cells showed the characteristic
clear, oval o r crescentic juxtanuclear area; iii some of the
cells this lighter-staining area completely eiicircled the nucleus. The nuclear menibrane was usually robust, with adherent coarse chroniatin blocks. The iiucleus stained deeply,
due to the relatively abundaiit inasses of chromatin. The
nuclei were relatively small, aiid generally held a peripheral
position. An occasional cell had a dense pyknotic nucleus ;
some of these cells were iii process of nueleai- extrusion. A
few cells were in process of amitosis as indicated by a lilobed
nucleus ; a few were binucleated, presuniablp the result of
nuclear ainitosis without subsequent cytoplasmic division. No
mitoses x-ere observed in this material, though mitoses had
been seen previously in siniiIar material ( .Toidan, ’29 : Jordan
and Morton, ’ 3 7 ) . Dubreuil and Favre ( ’21) ohserrecl initosis
in plasinacytes in the oiiieiituin of the rabbit, but claiiiied that
the process was always iiiconiplete aiid led oiily to hi- and
multi-iiuclea ted cells.
Scattered among the plasinacytes, especially toward the
liilar end of the iviedullary cords, o c c u r r d a few cells with
eosinophilic granules suggesting blood eosinophils, but with
typical plasniacyte spherical nucleus with “cart wheel” arrangement of the chromatin. There occurred a few similar
cells, but with larger eosiiiophilic spherides. Both of these
types of eosinophils represented presumably a variety of
Bussell-body cell. There were present also a few of the more
comnion type of Russell-body cell with one or several large
hyaline, acidophilic globules and a compressed or distorted
nucleus. Intermediate stages between plasmacytes with eosinophilic granules or spherules and cells with larger globules
mere not observed, though Dubreuil and Favre ( ’21) apparently demonstrated such transitional stages among plasmacytes in the omentuni of the rabbit. Still another type of
granular plasmacyte occurred ; here t h e granules wese relatively coarse and of variable shape, though generally spheyical. These granules took only a faint eosin stain, contrasting
328
HARVEY E. J O R D A S
sharply with the lirilliant red granules and spherules of
eosinophilic plasinacytcs. The nucleus was generally pyknotic
and peripherally placed. Some of these cells were in process
of enncleation, either by extrusion or intracellular resorption.
The granules of the resulting plastids were presumably
“degeneration granulcs” (Lewis, ’19). Plasmacytes with
either neutrophilic or basophilic granules were not observed.
Tisbue mast-cells uiirelated to plasmacytes occurred ; they
were larger than the plasmacytes, their cytoplasm was densely
packed with relatively large deeply-staining granules, and
the centrally located nucleus was relatively small and pyknotic.
The question of the origin of the plasmacytes in the medullary cords can be approached best by study of median longitudinal sections of the nodes. At the junction between cortex
a i d medulla could he seen transitional stages between the
predominating small lymphocytes of the cortex and the typical
plasmacytes of the medullary cords. The process was one of
growth of small lymphocytes to medium-sized lymphocytes,
corresponding to proplasmacytes, and subsequent transformation into plasmacytes. The histologic evidence from the
suhniaxillary lymph nodes seemed conclusive that here plasmacytes were derived exclusively from lymphocytes. The
cvideiice showed further that, though the stage of this cell
a s a typical plasniacyte was relatively stable and presumably
of considerable tenure, the eventual fate of the plasmacytes
was degeneration, with end-phases either as Russell-body
cells, acidophilic plastids with “degeneration granules, ” or
acidophilic non-granular plastids. The several transitional
stages from plasrnacytes with relatively large vesicular nucleus to plasmacytes with progressively smaller, more eccentric, and progressively more pyknotic nucleus to aiiuclear
plastids, closcly paralleled stages in erythrocytogenesis, leading from erythroblasts, through normoblasts to erythroplastids, and suggested an interpretation of plasmacytes as
abortive erythroblasts (Jordan, ’39 ; Jordan and IIorton,
’37).
T H E O B I ( ; I S .\XI) FATE O F PLASJSACPTES
329
Under the unitarian iiiterprctation of hemocytopoiesis it
might be assunied that given ccwtain conditioiis the aiicestral
lymphocytes followed an aberrant mode of diff erentlation
resulting in plasmacytes, mliich during further stages of
transformation produced aberrant plastids similar to erythroplastids but lacking hemoglobin, at least iii iiormal clieiiiical
condition ; and aberrant granulocytes similar to cosiiiophilic
leukocytes, but with abiiormal or possibly specifically functional granules. The nucleus of these granulocytes differed
marlredly from that of genuinc Mood eosinophils, and the
( igranules '' were larger " spherules. "
The concept of the developmental pluripotentialitv of
lyinphocytes as advocated most consistently by 11axiiiiow
('09) and Bloom ('37) has recently received added support
in experiments by Farr ('51) in which labeled lymphocytes
of the rabbit, autogenously transfused, were traced to the
lione iiiarrow where they became myelocytes. I n Bloom's
experiments, where lymphocytes from the thoracic duct of
rabbits previously immunized with Ascaris extract \\-ere
studied i n tissue cultures, the lymphocytes became transformed after from 5 to G days into heterophil (pseudoeosinopliil) leukocytes. Similar results were reported by Latta and
.J ohnsoii ( '34) ; cells with eosinophilic granules appeared in
their cultures (with splenic extract) of mcsenteric lymphnode tissue of the alliino rat. T h e uiiitarian interpretation
of lieinocytopoiesis is even iiiore clearly indicated for hirds.
Lymph nodes are lacking in birds, but the bone m a r r o v coiitaiiis iiumerous lymphoid nodules. The other chief source of
lymphocytes in birds is the spleen. Following splelicctoiny
in pigeons the number of marrow lymph-nodules was increased
( J o r d a n and Robeson, '4.3). The lymphocytes of these nodules
cliff erentiated into erptlirocytes within veiious sinuses ; estravascular lymphocytes differentiated into granular leukocytes.
The appearance of the characteristic clear juxtanuclear
area of typical plasmacytes, concomitant with the transformation of lymphocytes into plasmacytes, seemed in soiiie
way related to the progressire decrease iii size, peripheral
330
HARVEY E. qJORDAK
displaceiiient, and progressive pylinosis of tlie nucleus. This
clear area contains the cytocentruni and the Golgi apparatus
(hlaximom, '28 ; ,Jordan, '29). Supravital staining with Janus
green and neutral red disclosed also that both mitochondria
arid neutral red granules and spherules were in part aggregated about the controsome in this same area. Nuclear coiicentration was presumably accompanied by passage of fluid
into the pcrinuclear cytoplasm. On the assumption that the
cytocentrum, with the associated Golgi apparatus, constituted
an area of relatively less resistance to fluid seepage, the clear
juxtanuclear area of plasmacytes could be interpreted in
terms of dilution of the cytoplasm of this special region.
Subnaoxilliuy lymph n o d e s of inzintrtzrre cilbirzo r o t s
I n order to pursue further the problem of the origin of
plasniacytes it seemed desirable to study conditions in very
young animals. Sections of the suhmaxillary lymph nodes of
albino rats of 30 days gave precise and important data. Figure 2 shows a region of the medulla, including a median
lyniph sinus filled largely with small lymphocytes, bounded
on each side by a medullary cord. The cells of the cords
included many large cells with a relatively large, leptochromatic nucleus and a slightly basophilic cytoplasiii (fig. 13).
The nucleus of these large cells contained one or several
nucleoli. The nuclear membrane was rohust, with many adherent chromatin granules. These cells represented plasniablasts. They appeared identical with the relatively few
lyinphoblasts scattered among thc predominating small
lymphocytes of the cortex, and with those of the fex7 initial
cwrtical nodules.
more abundant cell was one of smaller
size, corresponding to a proplasmacyte. Here the relatively
smaller nucleus was characterized by a coarse membrane with
adherent larger chromatin blocks, lout generally lacked a
nucleolus. These cells showed tlic characteristic juxtanuclear
light area and many were in mitosis (fig. 13). A few of these
cells gave evidence of complete division, producing smaller
definitive plasmacytes ; a few remaiiiccl binucleated. The
THE O R I G I S A S D FATE O F PL4SiVIACYTES
331
proplasmacytes derived as daughter cells of plasmablasts
in the iiodes of 30-day rats were very similar to the proplasmacytes derived by growth of small t o medium-sized lymphocytes in the nodes of mature rats. This fact is in accord with
the lymphocyte genetic cycle : small lymphocytes grow to
become large lyniphocytes (lymphoblasts, plasmablasts)
which divide to forin medium-sized lymphocytes, and the
latter divide to form small lymphocytes.
In certain areas of the cords definitive plasmacytes were
abundant. I n these cells the nucleus was generally located
near the periphery. The cytoplasm was homogeneous, giving
a “vitreous” appearance; in a few cases it appeared very
finely granular. The shade of color varied from light blue t o
pink with hematosyliii and eosin; cells with the larger, less
chromatic nucleus had a bluish cytoplasm; those with smaller,
more chromatic or homogeneous, pylmotic nucleus had a pink
or light-orange color, suggestive of normohlasts. Included
among these predominating types of plasinacytes were also
a few of the following varieties: (1) plasmacytes with brilliant eosinophilic spheyical granules ; (2) plasmacytes with
small pachychromatic eccentric nucleus and with pale, acidophilic degeneration granules ; (3) plasmacytes with eosinophilic spherules and peripheral oval o r crescentic nucleus,
granular Russell-body cells ; (4) typical Russell-body cells
with several large hyalinc, eosinophilic glohules, and a defornied central or peripheral nucleus.
Conditions in the smaller submasillary nodes of rats of
15 days were similar to those in the larger nodes of 30-dayold rats, except that the medullary cords xTe1-e considerably
shorter and the lymph sinuses relatively wider, and Russellbody cells with large eosinophilic hyalinc globules were considerably more numerous.
illzr 1t i p 1e n?y e 1o m a . C o m 11 nct tzii n o r of cl avid e
Conditions in a small compact plasmacytonla removed from
the sternal end of the left clavicle of a patient with multiple
myeloma are illustrated in figures 3, 4, 5, 14, and 15. The
332
H S R V E P E. JORDAN
predominating cells were plasmacytes of various sizes (8 to
18 p in diameter) and in various stages of “maturity.” Some
of the larger of these cells had a nucleus with a chromatin
arrangement suggestive of the prophase stage of mitosis.
S o cells seemed to correspond to ancestral plasmablasts, but
many cells could be classified as proplasmacytes. A few of
the plasmacytes mere characterized by a relatively small
pyknotic, peripheral nucleus, suggesting a n early stage in
enucleation. Some of the cells mere very large, occasionally
with two or three nuclei. One cell was observed in mitosis,
a telophase stage. Amitosis was suggested in the case of a
few cells with a bilobed nucleus. One case of almost complete aniitotic division was observed ; here the nuclei of the
prospective daughter cells were coiinected by a delicate chromatic strand through a narrow cytoplasmic bridge. No
lymphocytes could be discriminated among the cells. The
questioii of the origin of the plasmacytes in this tumor became a matter of central interest. The clue to the solution
of this problem appeared in the capsular, endosteal region.
Here the coiinective tissue had assumed the character of a
loose mesh ; fibroblasts separated from the stroma, changed
from fusiform to sphcroidal shape, and took on the features
of typical plasma cells (fig. 4 ) . Similar small areas occurred
i n certain other regions of the tunior. On the basis of ahundant transitional forins between the constituent endosteal
fibroblasts and free plasniacytes, the conclusion seemed warranted that in this tumor the ancestral plasmablasts were
fibroblasts, possibly in part reticulum cells. The fact that
even a few mitotic and amitotic divisions occurred in this
tunior at this stage suggests that growth was in part a
process of proliferation among the plasmacytes.
Certain deeper regions of this tumor, characterized by
extensive degeneration, were of special interest. Here the
arrangement of the plasinacytes had hecome less conipact
(fig. 5). The prevailing cells had a relatively small, ppknotic,
generally eccentric nucleus. The cytoplasm was characterized
by coarse acidophilic spheric granules. N a n y of the cells
were in process of karyorrhexis (fig. 15). Scattered among
the cells were anuclear granular plastids. The suggestion
presented itself that the granules of these degenerating plasiiiacytes might bc related to the Beiice-Jones proteinuria
present in this patient, and at various tinies in patients with
multiple myeloma.
M u l f i p l e mjelomtr. CostuE marrow tumor
I n figure 6 is shown in section a region of rib mari-ow from
a case of multiple iiiyelonia with Bence-Jones proteinuria.
The predominating cells here also were typical plasmacvtes,
including a few that could be classified as plasmablasts and
pi-oplasniacytes. One of the cells, showii at the upper left
border of figure 11, had a bilobed nucleus, suggestive of
ainitosis. S o mitosis was observed. Scattered throughout
this region were a few degenerating cells and aiiuclear granular plastids. Several areas of similar regions showed large
aggregations of acidophilic granular plasmacytes in various
stages of disintegration, identical with those illustrated in
figures 5 and 15. I n these sections of this niarrow the more
interesting problein again concerned the origin of the plasmacytes. No lymphocytes were observed among the plasmacytes, and no transitional stages could be traced between
the stroinal reticulo-endothelium and plasmacytes. Ho\wvei*,
very suggestive evidence appeared in regions of apparently
normal erytlirocytogeiiesis, adjacent to and continuoii~with
compact areas of plasmacytes, that here the ancestral cells
were heinocytoblasts which functioned a s plasmablasts and
became transformed into plasmacytes.
Certain venous sinuses in such transitional regions contained typical hemocytohlasts, cells with relatively large leptochromatic nucleus throughout which were scattered sniall
chromatin granules. Adjacent sinuses contained predominantly plasmablasts with a few transitional stages het-v;een
hemocytoblasts and plasmablasts (fig. 7 ; a, fig. 6 ) ; others
contained a few similar plasmablasts and all the later stages
334
HARVEY E. J O R D A S
in erythrocytogenesis : erythroblasts, normoblasts and erythroplastids (fig. 8 ; c, fig. 6). The plasmablasts were somewhat
smaller than the typical hemocytoblasts, and their nuclear
chromatin comprised some larger, angular blocks (fig. 16).
Adjacent to the latter type of sinuses were such as contained
a predominance of plasmacytes with a few cells of the erythrocytogeiiic series (fig. 9 ; b, fig. 6), and such as contained
only plasniacytes of various sizes (fig. 10; d, fig. 6 ) ) these
mwging with tumor areas like those illustrated in figure 11
(e, fig. 6). I n these tumor areas it was noted that as the
plasmacptes became older, as evidenced by a shrinkage and
pykiiosis of the nucleus, the cyotplasm changed from a lightly
basophilic staining reaction with hematoxylin and eosin to
an acidophilic reaction; from a light blue color to light red
o r orange color.
X u 1 tiyle m?jel o ~ I a.
I
As pirut c.d st crnnl rnarrozv
Fresh mounts of aspirated sternal marrow from a patient
with multiple myeloma contributed additional data, especially
as concerned mobility of plasmacytes. This material contained iiumerous cells which could be classified as plasmablasts, proplasmacytes and definitive plasmacytes. There were
present also a few heinocytoblasts and all of the later stages
of erythrocytogenesis. In smears stained with Wright’s stain
the cytoplasm of the pouiiger plasmacytes stained a deep blue
color, that of older plasmacytes a light blue color. The cytoplasm of these plasmacytes contained numerous granules. On
supmrital application of Janus green and neutral red some
of these granules staiiied blue-green, others light red. The
blue-green “granules, ” consisting of a few rods and more
numerous spherules, were obviously mitochondria. Some of
the plamacytes protruded one o r several short, stout pseudopods, and exhibited a slight degree of motion; some assumed
an irregular form, commonly an elongate oval shape, with
the nucleus a t one end, signifying a capacity for a slight
degree of ameboid movement. This slight mobility was similar
to that exhibited by the plasmacytes from the submaxillary
THE ORIGIN AND FATE O F PLASMACYTES
335
lyniph nodes of the albino rat observed over long periods in
chickeii plasma mounts under sealed coverglass. The type
of plasniacyte motility in these preparations from lymph
nodes of rats contrasted sharply with the more vigorous
arneboid mot ion of the lyniphocy t e s.
UISCUSSION
The principal locations in which plasmacytes appear under
normal conditions in mammals are lymph nodes, spleen, thymus, hone marrow, omentum and the intestinal mucosa. Plasmacytes occur in relatively large numbers in the medullary
cords of lymph nodes, especially in the submaxillary nodes.
In the spleen, thymus, omentuni and intestinal mucosa the
plasinacytes are scattered ; in bone marrow they are generally
scattered but may appear in small groups. The possible
sources of origin of the plasmacytes in these tissues and
organs are reticular connective tissue and lymphocytes. Since
the evidence for lymphocyte origin in lymph nodes, based on
transitional stages, appears conclusive, it seems probable that
in the spleen, thymus, bone marrow, omentum and intestinal
mucosa plasmacytes arise only from lymphocytes. This assumption is in accord with Maximow's ('28) observation that
in his tissue cultures lymphocytes became transformed into
plasmacytes toward the end of 48 hours. As regards the
thymus, the probability of exclusive origin of plasmacytes
from lymphocytes is enhanced by the fact that here mesenc1i;vmal reticular stroma is relatively sparse, practically restricted to the smaller blood vessels, while plasmacytes are
widely scattered among the cortical thymocytes (lymphocytes)
of the lobules.
Considering the question of a possible differential factor
determining whether plasmacytes appear in aggregations or
are scattered, the outstanding datum concerns the amount of
lymph supply. It is generally held that lymphatics are lacking
in the splenic parenchyma of man and other mammals. H 0 ~ 7 ever, Snook ('46) has described deep lymphatic plexuses in
the spleens of guinea pig, mole, mouse, horse and monkey.
336
HARVEY E. J O R D S S
Thc content of lymphatics in the spleen generally inal- be
considered meager. Lymphatics a r e also relatively scanty
in the thymic parenchyma and i n bone marrow. Since lynipliatics a r e abundant in the intestines, oinentuni and l;Vmph
nodes, further search must be made for a differential factor
a s between lymph nodes, where plasmacytes may occur in
the niedulla i n large masses, and the omeiituni and the intestines where they occur relatively scattered. The cardinal
differential datum in comparing these areas concerns the
relatively large lymph sinuses of the medulla of lymph nodes.
On further consideration of this datum there appears the additional factor of relative lymph stasis. That lyniph stasis
may be a n important differential stimulus to lymphocyte
transformation into plasmacytes is supported by two esperiineiits reported in earlier publications (Jordan, IGndred and
Paine, '31; J o r d a n and Moi-ton, '37). Tn kidneys of rabbits
mliere the major blood vessels and adjacent lymphatics had
been ligated for 8 weeks, the ensuing renal necrosis was accompanied by the appearance of numerous plasmacytes and
their transformations a s Russell-body cells. I n dogs, where
a segment of the lower portion of the thoracic duct had been
isolated for from 4 to 30 days by a double ligature, lymph
nodes below the level of ligation showed dilated eft'erent
lymph vessels containing niaiiy plasmacytes, sonic in mitosis.
In these experiments there obviously must have occurred an
accumulation of noxious metabolites, and one is led to tlic
conclusion that a fundamental factor in stimulating N transformation of lymphocytes into plasniacytes was some form of
toxin.
A t this point one faces the problem of finding a coniiiioii
factor among pathologic areas cliaracterized by an accumulation of plasmacytes : areas of chronic inflammation IT-ith
lyniphocyte infiltration, degenerating areas, and various tunioi-s, including multiple myeloma. Here, also, the results
of the two experiments cited above niay have explanatory
application in terms of lymph stasis a i d the accumulation of
noxious metabolites. IIowever, in the case of multiple m p -
THE O R I G I S A N D FATE O F PLASMACPTES
337
loma an additional factor must be postulated, since here the
original plasmablasts become transformed into neoplastic
cells. lloreover, in tumors of multiple myeloma, the ancestral
cells may be either fibroblasts, as in the case of the compact
subendosteal tumor of the clavicle ; or hemocytoblasts, as in
the case of the marrow tumor of a rib.
Without considering the superimposed neoplastic factor in
multiple myeloma, the question may profitably be pursued as
to why fibroblasts and hemocytoblasts as well as lymphocytes
respond with plasmacyte transformation under certain conditions. Here the lymph node material from 30-day-old rats
may give a clue. A s described above, the plasmablasts of the
medullary cords in these nodes appear identical with the
lymphoblasts scattered throughout the cortex and resident
in the initial small cortical nodules. The lymphoblasts originated from cells of the reticular stroma, slightly modified
initial mesenchyme. The connective tissue of the endosteum,
with its fibroblasts, also had initial origin from mesenchyme.
Certain fibroblasts may have retained initial lymphoblast
potentialities, or dedifferentiated to stages with such potentialities. I n the bone marrow the hemocytoblasts, at least very
similar cytologically to lymphoblasts and plasmablasts, arose
from cells of the reticulo-endothelium or free lymphoid derivatives. The transitional stages between hemocytoblasts in
the erythrocytopoietic venous sinuses and plasmablasts of
adjacent sinuses, and between the latter and the plasmacytes
of the adjacent plasmacytoma, as shown in figures 7, 8, 9, and
10, support the conclusion that here the plasmacytes represent
transformations of hemocytoblasts (fig. 16).
The most plausible explanation for these multiple sources
of plasmacyte origin under different conditions would seem
to be in terms of the unitarian theory of hemocytopoiesis
which postulates an identity among hemocytoblasts, lymphoblasts and plasmablasts, each with multiple developmental
potentialities. Taking into account overlapping minor cytological variations among these three groups of primitive cells,
they appear identical. All three trace their source of origin
338
HARVEY E. JORDAN
to original mesenchyme, through reticulo-endothelial cells aiid
their developmental niodifications as histiocytes, fibroblast s
or polyvalent lymphoblasts.
SUMMARY
I n the inaterial of this investigation plasmacytes originated
from different ancestral cells : in the sulnmaxillarg l?-mph
nodes of adult albino rats, from medium-sized lyiipliocytes
at the distal border of the medullary cords; in rats of 3 3 and
30 days, froni large lymphoblasts (plasmablasts) in the medullary cords ; in a subendosteal plasmacptoma of the clavicle in
H case of multiple myeloma, from fibroblasts ; in cost.cl1 lllarro\\’
froni another case of multiple myeloma, from heiiiocytoblasts.
The variable origin of plasmacytes in different tissues uiidcr different conditions may be explained in terms of the
unitarian theory of hemocytopoiesis which ascribes to the
lymphocytes and their ancestral reticular connective tissue
iiiultiple developmental potentialities, the end result determined by differential eiiviroiirneiital conditions. Heniocptoblasts, plasmablasts and lymphoblasts appear cytologically
identical aiid may be coiisidered as having identical polyvalent
developmental capacities depending upon specific enrironmental stimuli. I n neoplastic conditions involving plasniacytes an additional factor presumably becomes operative.
Young plasinacytes in lymph nodes divide by mitosis, older
plasmacytcs divide by amitosis ; both forms of division may
stop short of cytoplasinic division, producing bi- or multinucleated cells. Only several mitotic figures and only one
almost complete amitotic division were observed in the plasmacytomas of this investigation, but binucleated cells and
cells with bilobed nuclei were numerous, arid tri- and quadrinucleated cells occurred.
Russell-body cells were not seen in these plasniac;vtomas,
but there occurred large areas of otherwise degenerating
plasmacytes. These plasniacytes were characterized by coarse
acidophilic, generally spherical, granules and a disintegrating
nucleus. The suggestion presented itself that this cytoplasmic
T H E ORIGIX A X D FATE O F PLASMACYTES
339
granular material might have some relation to the BenceJones proteinuria of multiple myeloma.
Plasmacytes in fresh mounts in chicken plasma, under
sealed coverglass, from submaxillary lymph nodes of albino
rats, and similar preparations of heparinized aspirated sternal
marrow from a patient with multiple myeloma, exhibited a
slight degree of motility characterized by protrusion of one
or two short blunt pseudopods and a change of shape from
spherical forin to elongate oval with the nucleus placed at
one end.
LITERATURE CITETJ
BLOOM,
W.
1928 The relationship between lymplioeytes, monorytes and plasma
cells. Folia haemat., 37 : 63-69.
1937 Transformation of lymphocg tes into granulocytes i n vitro.
Anat. Ree., 69 : 99-116.
CAMPBELL, B., AND R. s. GOOD 1949 Antigen-antibody mechanisms in neurotropic virus diseases. Anat. Rec., 2 0 3 : 16. (Abstract Proc. Am. Assn.
Anat.)
CUSTER, R. P. 1949 An Atlas of the Blood and Bone Marrow. W. B. Saunders
Co., Philadelphia.
DOWNEY,H. 1927 The myeloblast - its occurrence under normal and pathological conditions, and its relation to the lymphocytes and other blood
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1928 The Myeloblast. See. 12, Val. I, Special Cytology, pp. 371399 (Cowdry, E. V.). Paul B. Hoeber, h e . , New York.
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G., AND M. FAVRE1921 Cellules plasmatiques. Plasmazellen a granulations specifique: cellules a corps de Russell. Arch. D 'Anat. Yicr.,
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R. S. 1951 Experiments on the f a t e of the lymphocyte. Anat. Rec., 109:
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H. E., J. E. KINDRED
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340
HARVEY E. J O R D A S
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I
s. KAXTor, 1949 Recent studies of multiple
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PLATE 1
EXPLANATION O F FIGURES
1 Photomicrograph of an area from a stained section of a medullary cord of the
submaxillary lymph node of a 6-month-old albino rat. X 1530. (Compare
with fig. 12.)
2
Pliotomicrograpli of an area of the medulla from a stained section of the sn1)maxillary lymph node of a 30-day-old albino rat, including a median sinus
filled with small lympliocytes, and portions of the adjacent cords with conspicuous large plasmablasts, smaller proplasmacytes and definitive plasm:\cytes. X 1250. (Compare with fig. 13.)
I’LATK
341
1
PTATE 2
ESI’LASATION 0)’ FIGURES
3
I’liotoniicrograpll of :in :ilea fro111 ii stained section of a sm:rll tumor (plasmacytonia) surgically reniorcd from the s t c r ~ l a lelid of the left c l : ~ ~ i c l of
e ):
patient with multiple niye1om:i. X 1250. (Compare with fig. 14.)
4
From the s a n e sectioii as figure 3 , showiiig :it the left transformation of
fibroblasts i n t o plasm:icytes in the snbeiidosteal region. X 1250.
5
Photoiniciogr:~phof a11 area :id,jacriit to t h a t of figure 3. Here the pl:isnincgtes are in process of degeneration. They ’nave a relatirely small, pyknotic,
frequently disrupted nucleus. The acidophilic cytoplasmic granules take a
deep pink color with the hematoxylili eosiii stain. X 1250. ( C o n i p r e with
fig. 15.)
342
PLATE 2
343
PLATE 3
ESPLANATIOS OW 3”IGI:KES
6
Photomicrograph of a region of costal marrow from a case of multiple myeloma, showing transition from relatively normal marrow (below) t o a typical
plasinaeytoma. X 130.
7
Veiloris sinus (a, fig. 6) fillcd with cells intermediate between hemocytob1:ists
and plasmablasts. X 1250.
8
Venous sinus ( c , fig. 6) filled 11-it11 a v:criety of cells incliiding mostly 1101nioblasts and a few plasmacytes. X 1250.
9
Vt~iioiissinus (b, fig. 6 ) filled vitli :I variety of cells inrluding proplasni:tcytes,
plnsni:ic~ytesand normohlasts. X 1250.
10
Area of disrupted renous sinus (d, fig. 6 ) showing 5 typical largc p1;isniacytrs
(‘ myeloma cells ”) and soine smaller plasmacytes. x 1250.
11 Compact : x e a of plasmacgtoina (e, fig. 6 ) . A plasmaeyte ( u p p w left) i s i n
process of nuclear ainitosis. x 1250.
344
TTIE O R I G I N AND FATE: Oh’ P L A S M A C Y T E S
PLATE 3
I € h R V X Y R . J011T).\hi
345
12
1)r:iwiiig of n collection of sclcc*ted cells froni a regioii similar to that of
figure 1, including aniong typic;il pl:ismacytes t w o (a, b ) in process of aniitosis, one (c) with t v o nuclei, one ( d ) in process of enuclcation, :ind on(: ( e )
n.itlr eosinopliilic spherules, a tylw of RusseIl-boclT cell. X 1600.
I.:{ 1)r:iwiiig of n colleetioii of selected cells froni
:I niednllary cord of tlrc s i i b
~ii;isillarylympli node of R 30-dayold albino nit (fig. 2 ) . The cells include
two p1:isnia.blests ( a ) , se\-er:il prop1asm:tcytcs (11, three in mitosis), several
tyl)ic:il p1:isnineytes ( c ) witli cwcntric nucleus and juxtniiuclear cle:ir area,
olio older plasinacyte with sm:ill, pyknotic nnclens ( d ) , and one R,usscll-l)ocly
cell with rosinopliilic splicriiles (e). X 1600.
14
Urawiiig of n collection o
Iected cells f i w n : i n aro:i of the eonlpact p1asin:icytoni:! siniihr t o that of figii~cs3 and 4. The large biiiuclcated cell ( p ~ o p1asni;rcyte) slrors :i sliallow medi:il constrietioii, suggesting a n early stage
in cytoplasmic division. X 1600.
1.5 l>r;iiving of a collect.ion of selwted cells froin t i n nren of the compact pl;1s1ri:lcytoni;i siniilar to that of figiuc 5, showing progressive stages ill karyorrhesis.
x
1600.
16 Drawings of :t progressive serirs of cells in the transforn~ation of a lremocytob1:ist (a) to a definitive plasnincyte ( f ) . 11, p l n s ~ ~ ~ b l a c,
s t ;d ;illti e,
proplnsmacytes. x 1600.
346
T H E O R I G I N A N D FATE OF PLASMACYTES
HARVEY E. JORDAN
347
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