The fine structure of connective tissue

EXPERIMENTAL

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MOLECULAR

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PATHOLOGY

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535-553

Structure II.

HENRY

1,

Z.

of

Connective

The Plasma

MOVAT

Department University

(1962)

of of

AND

Pathology, Toronto,

Received

June

Cell’ V. P.

NEIL

Tissue

Banting Toronto,

FERNANDO~ Institute, Canada

9. 1962

INTRODUCTION This paper deals with the fine structure of the mature plasma cells which occur in connective and lympho-reticular tissue. These cells have a dense, eccentrically located nucleus, deeply basophilic cytoplasm, and a low nucleo-cytoplasmic ratio. They have sometimes been designated plasmacytes or plasmocytes. The immature forms which are sometimes called proplasmacytes or plasmablasts, and which have a higher nucleo-cytoplasmic ratio, large nucleoli and less eccentric nuclei will be described only briefly. They will be dealt with in more detail in another publication which will deal with the maturation and origin of the plasma cells. MATERIALS

AND

METHODS

Plasma cells occur in varying number in healthy humans and animals. They are normally common in lympho-reticular tissue and in the submucosa of the intestine, but become very numerous in several tissues following antigenic stimulation. Most of the material in the present study was, therefore, obtained from immunized animals. Rabbits and hamsters received repeated intravenous, intraperitoneal or intraarticular injections of horse serum, and the plasma cells so induced were studied in the spleen, omentum, mesentery, articular and periarticular connective tissues, Plasma cells in spleen, mesenteric lymph nodes, omentum, mesentery and hamster cheek pouch from untreated animals were also studied. Since there was no difference in the morphology of the plasma cells of immunized and nonimmunized animals, a single description will suffice. Fixation, dehydration, embedding and staining were as described in detail by Movat and Fernando (1962). An RCA-EMU-3E electron microscope was used throughout the study. RESULTS GENERAL

FEATURES

Mature plasma cells have a characteristic appearance when observed with the light microscope. They are usually round or oval, though, when squeezed between other cells and fibers, they may be quite irregular in shape. The dense nucleus is ec1 Supported by a grant from the Canadian Arthritis ment of Health and Welfare of Canada. 3 Research Fellow under the Colombo Plan. 535

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Rheumatism

Society

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the Depart-

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FERNANDO

centrically placed and characteristically has clumped chromatin. The cytoplasm is intensely basophilic, and intensely pyroninophilic. A perinuclear halo or clear area is seen in most cells. Plasma cells may be found singly, but more commonly they occur in groups, both in lymphoid tissue and in loose connective tissue (Fig. 1). In the latter case, they are found in the vicinity of vessels (Fig. 2). In low magnification electron micrographs (Fig. 3), it can be seen that the basophilia of the cytoplasm as seen with the light microscope corresponds to a well

FIG. 1. Accumulation of p!asma cells (PC) in synovial connective articular injection of horse serum. Syn. = synovial lining. Formalin fixed, and methyl green-pyronine stained section, 3 u thick, x 390.

tissue, following intrametharrylate embedded

FIG. 2. Plasma cells between two venules (VEN) and a capillary (CAP) of the mesentery of a rabbit which had received multiple intraperitoneal injections of horse serum. Note the dilated rough surfaced vesicles of the endoplasmic reticulum in the cells marked with arrows. Osmium tetroxide fixated, Selectron-Methacrylate embedded, periodic acid-silver methenamine stained % u thick section, X 975.

FIG. 3. Low power electron micrograph showing a deeper cut through the area shown in Fig. 2. This is a fairly thick section and therefore the condensation of chromatin at the periphery of nuclei is pronounced in the plasma cells (PC) and a lymphocyte (Ly). Nuclei of a fibroblast (Fb) and a macrophage (Mac) are paler. Some plasma cells, but particu!arly the one in the center, have a dilated ergastoplasm (der). The Golgi region (gol) is prominent in several cells below the venule (ven) and in the cell below the center. BM = basement membrane; Co1 = collagen fibrils; Cap = capillary. Selectron: Methacrylate 8: 2, periodic acid-silver methenamine, X 3200.

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FIG. 4. A mature plasma cell from articular connective tissue. The nucleus (nut) shows the condensation of chromatin at its periphery. The Golgi apparatus is small in this plane of sectioning. Note typical ergastoplasm consisting of rough surfaced vesicles (rsv), which reach to the periphery of the cell, mitochondria (mit), a dense body (db), a few smooth surfaced vesicles (SW), and occasional micro villi (vil) at the cell border. Selectron: Methacrylate 5: 5, uranyl acetate, X 24,400.

FIG. 5’. Immature plasma cells from the spleen (white pulp) of a rabbit which 72 hours previously received a large intravenous injection of horse serum. Such cells are the morphological counterpart of an early (secondary) immune response. The cell in the center is a plasmablast (PB). Its nucleus (nut) has the well known nuclear pores (arrow), and contains a large nucleolus (ne) There is a high nucleo-cytoplasmic ratio. The cytoplasm contains abundant free ribonucleoprotein

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particles (mp), mostly in clumps. There are a few rough surfaced vesicles (rsv). The (PPC) to the right contains more ergastoplasm (er), and numerous mitochondria cell membrane; Epon, lead hydroxyde, X 20,000. FIG. 6. Part of an immature plasma cell. Note (rnp) and small Russell bodies (rb) in rough surfaced pore. Epon, lead hydroxyde, X 52,000.

numerous free ribo-nucleoprotein vesicles (rsv). The arrow points

539

proplasmacyte (mit). cm = particles to a nuclear

FIG. 7. Plasma cell from articular tudinally and slightly obliquely cut ergastoplasm. Selectron: Methacrylate

connective tissue. A diplosome is seen consisting of longigo1 = Golgi area; er = centrioles (ten) ; nut = nucleus; 5: 5, lead hydroxyde, X 52,000.

FIG. 8. Plasma cell from the same source as those shown in Figs. 5 and 6. The Golgi area contains a centriole (ten) in the center surrounded by globules (glob), tubules (tub), and vesicles (ves). At the arrow there seems to be continuity between a rough-surfaced and a smooth-surfaced vesicle. Both contain a dense material. er ergastoplasm; mit = mitochondria. Epon. many1 acetate, X 40,000. 540

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FIG. 9. Golgi region of a mature plasma cell. Note particularly the dilated membrane bound vacuoles (vat), which appear continuous with the flat tubules (tub) and a moderately dense irregular structure (arrow). nut = nucleus; ves I vesicles; mit = mitochondria; er = ergastoplasm; vi1 = villus. Selectron: Methacrylate 5: 5, lead hydroxyde, x 34,400.

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FIG. 10. The Golgi area in this cell from the same source as that shown in Fig. 4 has parallel membranes or tubules (tub) at the periphery and irregular, moderately dense bodies with ill-defined limiting membranes in the center. Note several dense bodies (db) at the periphery of the cell. Labelling of remaining structures as in previous micrographs. Selectron: Methacrylate 5: 5, lead hydroxyde, x 37,400.

FIG. 11. Plasma cells (PC) and a fibroblast (Fb) from mesentery of a rabbit given multiple intraperitoneal injections of horse serum. The Golgi complexes (gol) of plasma cells contain many dense, silver-positive globules (glob). Selectron: Methacrylate 8: 2, periodic acid-silver methenamine, X 7500.

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FIG. 12. Cells from the same (glob) range in size from that of components are tubules (tub) and a rough surfaced vesicle and the x 20,200.

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source as in previous micrograph. Note that the dense globules a vesicle to roughly half of that of a mitochondrion. Other Golgi vesicles (ves). At the arrow there seems to be continuity between extra-cellular space. Selectron: Methacrylate 8: 2, uranyl acetate,

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developed ergastoplasm (rough surfaced perinuclear halo or clear area coincides apparatus. The cell shown in Fig. 4 is a typical cept perhaps that the plane at which it the Golgi area. THE

CELLULAR

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V. P. FERNANDO

vesicles of the endoplasmic reticulum.) The with the location of a well developed Golgi plasma cell as seen at high magnification, exhas been cut does not show the full extent of

COMPONENTS

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The nucleus of mature plasma cells stands out as one of the densest of mesenchymal nuclei (Fig. 3). There is slight or marked condensation of the chromatin at the periphery of the nucleus, giving it the well known ‘(cart-wheel” appearance (Fig. 3). Of the two nuclear membranes the outer one is covered by RNP-particles (Fig. S), and is continuous with cytoplasmic rough surfaced vesicles (Fig. 12). Nuclear pores occur in the plasma cell, as in other cells (Figs. 5 and 6). Well developed nucleoli are found only in immature cells (Fig. 5). Centrioles are similar to those in other cells (Figs. 7 and 8). A diplosome is sometimes seenbeside the nucleus (Fig. 7). The Golgi apparatus stands out in most cells. It is well seen even at low power in sections impregnated with silver methenamine (Fig. 3). The Golgi area consists of small vesiclesand parallel membranesor tubules (Figs. 9, 10, and 12), the tubules being most common around the periphery of the area. The tubules often dilate to form vacuoles (Fig. 9). Other structures, round or irregular, have a homogeneous moderately electron densecontent with a slightly denser periphery and an indefinite limiting membrane (Figs. 9, 10, and 13). Yet another component is an electron dense homogeneousglobule (Figs. 8 and 12), the contents of which stain well with Protargol (silver proteinate) (Fig. 14), and particularly well with silver methenamine after periodic acid oxidation (Fig. 11). Mitochondria are more prominent than in other mesenchymal cells and occur in relatively large numbers between the ergastoplasmicsacs.They are oval and have the usual internal structure found in cells of mesenchymalorigin (Figs. 4, 5, and 16). Round to oval dense bodies (“cytosomes”) are common in plasma cells (Figs. 4, 10, and 15). They are smaller than mitochondria, ranging from 0.4 to 1 p in diameter, are electron dense,and contain an eccentric denser portion, or laminated membranes. Both these, the internal membranesand the limiting membrane of the bodies show the unit membrane structure. The bodies are probably microbodies or lysosomes. FIG. 13. In this Golgi area there are in addition to tubules (mvb). The arrow points to a dense structure described in Fig. tion. Selectron: Methacrylate 5: 5, lead hydroxyde, X 28,000.

and vesicles multivesicular bodies 9, and probably lipid in composi-

FIG. 14. A plasma cell from the articular connective tissue. In (glob) and tubules (tub) contain a homogeneous dense substance. Protargol, X 26,400.

the Golgi Selectron:

region both Methacrylate

globules 5: 5,

FIG. 15. High magnification of a dense body such as those shown in Figs. 4 and 10. The oval structure is limited by a unit membrane consisting of two dense lines separated by a light space (arrows). The interior is dense, faintly granular and contains several parallel membranes. Articular connective tissue. Selectron: Methacrylate 5: 5, many1 acetate, X 129,800.

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The ergastoplasm is more highly developed than in any other connective tissue cell. There is no clear peripheral zone as in fibroblasts, the ergastoplasmreaching to the periphery of the cytoplasm (Fig, 4). In immature cells (Fig. 5, PB), there are only a few ergastoplasmicsacs,but as the cells mature (Fig. 5, PPC) they become more numerous to reach their full development of maturity (Fig. 4). In mature cells, both flat and dilated rough surfaced vesiclesare encountered (Fig. 3). Figures 16 and 17 show in detail the structure of the ergastoplasmicsacs.The cavity contains a floccular material, and the limiting membrane is irregularly covered by RNP particles. When dilated, the sacs may contain a dense amorphous material in the form of small globules which occupy only part of the sac (Fig. 6), or which fill it to its margins (Figs. 18 and 19). The larger globules correspond to Russell bodies. Occasionally crystalline material is encountered in dilated sacs(Fig. 20). The crystals are cylindrical and show a periodicity of approximately 120A (Fig. 21). The cell membrane has the unit membranestructure, as is seenbest in villi (Fig. 17) which are randomly distributed (Fig. 4) around the cell. The hyaloplasm contains numerous free RNP particles (ribosomes) in immature plasma cells (Figs . 5 and 6)) but relatively few are encountered in mature cells (Figs. 17 and 21). Filaments are seenin the hyaloplasm only occasionally (Fig. 16). DISCUSSION Plasma cells were first described by Unna ( 1891, 1913)) Pappenheim ( 1901)) and independently by Cajal (1906). Pappenheim (1901) attributed their intense basophilia to the high concentration of ribonucleoprotein (“paranucleoproteid”) in the cytoplasm. Their function has only been elucidated during the last two decades. Huebschmann (1913) did suggestsometime ago that plasma cells might be antibody producers, but it remained to Scandinavian investigators (Bjorneboe and Gormsen, 1943: Fagraeus, 1948) to show clearly the relationship between plasma cells and antibody. The earlier studiesin Scandinavia were soonconfirmed and extended (Ehrich et al., 1949)) and direct evidence was obtained that plasma cells contain and probably manufacture antibody (Reiss et al., 1950; Moeschlin and Demiral, 1952; Coons et al., 1955; Nossal and Lederberg, 1958; Nossal and Mlkell, 1962). Subsequently it was shown that plasma cells in human lymph nodes contain gamma globulin (Ortega and Mellors, 1957), and that those in synovial tissue and lymph nodes of patients with rheumatoid arthritis contain the rheumatoid factor (Mellors et al., 1959). It was also shown that plasma cells are prominent in the connective tissue in

FIG. 16. The mitochondria (mit) shown in this micrograph other mesenchymal cells. The ergastoplasm (er) contains (drsv). Note a few filaments (fil) in the hyaloplasm, above crylate 5: 5, lead hydroxyde, X 40,000.

are typical of plasma cells and most some dilated rough surfaced vesicles the nucleus (nut). Selectron: Metha-

FIG. 17. Details of numerous ergastoplasmic sacs or rough surfaced vesicles of a mature plasma cell. Articular connective tissue. They have a limiting membrane (mem) and are covered on their outer surface, often incompletely, by ribonucleoprotein granules (rnp). Free granules (frnp) are seen between the vesicles. A villus is shown on the left. Both in the villus and elsewhere the cell membrane has the unit membrane structure (arrows). Selectron: Methacry!ate 5: 5, lead hydroxyde, x 63,600.

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FIGS. 18 and 19. Plasma cell from the omentum of an immunized rabbit. The Russell bodies (rb) in Fig. 18 stain intensly with silver methenamine after periodic acid oxydation. Figure 19 is a deeper cut of the same cell stained with uranyl acetate. Note that the Russell bodies completely fill the diIated ergastop!asmic sacs. The nucleolus (ne) in Fig. 19 indicates that the cell is relatively immature. Small globules (glob) in the Golgi area have about the same density as the Russell bodies. ten = centriole; Ly = lymphocyte. Selectron: MethacryIate 8: 2, Fig. 18, X 7300; Fig. 19, X 16,500. 548

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hypersensitivity reactions of the immediate type (Movat, 1956; More and Movat, 1959). Braunsteiner and co-workers (1953, 1955) were the first to show by electron microscopy that the cytoplasm of plasma cells is abundant in rough surfaced vesicles

FK. 20. Plasma cell from mesentery of rabbit immunized with multiple intraperitonea! injections of antigen. The nucleus (nut) is distorted due to compression by rough surfaced vesicles (rsv), which are mostly dilated (drsv) and contain numerous crystals sectioned longitudinally, obliquely or transversly. cm = cell membrane; hyl = hyaloplasm. Selectron: Methacrylate 5: 5. uranyl acetate, X 12,900.

(ergastoplasm). These 1956; Policard et aZ., 1958, 1960; Bernhard cellular structures were

findings were confirmed and extended (Amano and Tanaka, 1955; Wellensiek, 1957; Movat and Wilson, 1959; Thiery, and Gramboulan, 1960; Bessis, 1961). In addition, other described, the Golgi apparatus and centrioles (Stroekenius,

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1957a), Russell bodies (Stoekenius, 19.5713;Thiery, 1958; Welsh, 1962), and crystals (Wellensiek, 1957; Thiery, 1958; Bessis,1961). Of all mesenchymalcells, plasmacells have the most highly developed ergastoplasm. The rough surfaced vesicles reach to the borders of the cytoplasm and there is no ergastoplasm-freezone as in fibroblasts (Movat and Fernando, 1962). The ergastoplasmic sacs may be flat or dilated. They may appear empty, or may contain a granular material, dense droplets or crystals. Histochemical studies have shown that the granular material has, when condensed,the characteristics of a muco- or glyco-

FIG. 21. Higher magnification of the ergastoplasmic sacs seen in Fig. 20. The longitudinally sectioned crystals show repeating cross-banding (best seen between arrows) of approximately 120 A. frnp = free ribonucleoprotein granules, X 66,500.

protein (Pearse, 1959; White, 1954). It also seemsplausible to assumethat the denseRussell bodies are a higher concentration of this samesecretory product. It is, however, difficult to say whether Russell bodies are due to stagnation of the secretory product, or whether they are the result of enhanced secretion. The fact that Russell bodies develop when animals are hyperimmunized favors the latter possibility, though White (1954) observed that Russell bodies developed only upon stimulation with certain antigens. It is generally accepted that in all cells the synthesis of protein takes place in the rough surfaced vesicles of the endoplasmic reticulum. However it is still unknown how the synthesized protein leaves the cell. Epithelial cells which are known to manufacture and secrete protein have in addition to a well developed ergastoplasm,

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a well developed Golgi apparatus. Among the mesenchymal cells, it is the fibroblast and the plasma cell which have the largest and most complex Golgi areas. In the ‘(resting” fibroblast, the Golgi area is relatively small and circumscribed, but in proliferating fibroblasts it becomes more diffuse, and occupies a large area of the cytoplasm (Movat and Fernando, 1962). Plasma cells have at times an even larger Golgi region, though it is not as diffuse as in the fibroblast. Like the fibroblast the plasma cell has in the Golgi apparatus, in addition to the common vesicles vacuoles and flat sacs, rather prominent globules similar to Russell bodies, though much smaller. Like the Russell bodies, these globules stain with silver methenamine after periodic acid oxidation. We would like to suggest that the material produced in the ergastoplasmic sacs of plasma cells is segregated in the Golgi area for secretion and that this material may at times be seen as dense globules, in both the distended ergastoplasmic sacs and in the Golgi apparatus. At the cell border the plasma cell has finger like processes. Such structures were found also in mast cells (Fernando and Movat, 1963), and are quite numerous in macrophages (Fernando and Movat, 1963). These structures are generally regarded to be concerned with uptake of substances by the cell. In the case of the plasma cell or its precursor, it may be antigen, or more probably, partly catabolized antigen (Ehrich, 1955) furnished by macrophages which have taken it up. In any case the villous processes indicate that plasma cells are concerned not only with secretion, but also with uptake of substrates. SUMMARY The fine structure of plasma cells in lympho-reticular and connective tissue is described, When observed with the light microscope, mature plasma cells have a basophilic cytoplasm, a perinuclear clear area, and an eccentric dense nucleus. With the electron microscope, a well developed ergastoplasm and a large Golgi apparatus are characteristic of the cell. Immature plasma cells have well developed nucleoli, a relatively high nucleo-cytoplasmic ratio, and more abundant free RNP particles. In plasma cells, the ergastoplasmic sacs may be flat or dilated, When dilated they may contain a finely floccular substance, small dense bodies, large dense bodies (Russell bodies), or crystals. The Golgi area of plasma cells consists of small vesicles, flat or di!ated tubules, round or irregular structures with a dense periphery and an obscured limiting membrane, and dense homogeneous globules. The latter are simi!ar to, though much smaller than, the bodies or globules which occur occasionally in the rough surfaced vesicles (Russell bodies). Histochemical, in vitro, immuno-fluorescent studies and other evidence indicates that plasma cells produce antibody and other globulins. This theory is supported by the electron microscopic findings. ACKNOWLEDGMENT The authors wish to express their gratitude to Drs. A. C. Ritchie and J. W. Steiner for valuable help and criticism in preparation of this manuscript. Grateful acknowledgment is made to Miss Charlotte Turnbull, Miss Anneliese Wobser, Mrs. Ottie Freitag, and Mr. David Macmorine for their patience and ski11 in the preparation of the numerous sections examined in this study. Mr. Giinter Thomas was of invaluable assistance in the operation of the electron microscope. REFERENCES Further observation of the plasma cell generation from the AMANO, J., and TANAKA, H. (1956). vascular adventitial cells through metamorphosis by ultrathin sections under electron microscope. Acta Haematol. Jap. 19, 738-741. BARGMANN, W., and KNOOP, A. (1959). iiber die Morphologie der Milchsekretion. Licht und elektronenmikroskopische Studien an der Milchdriise der Ratte. Z. Zellfovsch. 49, 344-388.

552 BERNHARD, In “Ciba and M. BESSIS, M. antibody BJORNEBOE, antibody

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W., and GRAMBOULAN, N. (1960). Ultrastructure of immunologically competent cells. Foundation Symposium on Cellular Aspects of Immunity” (G. E. W. Wolstenholme O’Connor, eds.), J. and A. Churchill, London. (1961). Ultrastructure of lymphoid and plasma cells in relation to globulin and formation. Lab. Invest. 10, 1040-1067. M., and GORMSEN, H. (1943). Experimental studies on the role of plasma cells as producers. Acta Pathol. Microbial. &and. 26, 649-694. BRAURSTEINER, H., and PAKESCH, F. (1955). Electron microscopy and the functional significance of a new cellular structure. Blood 10, 650-654. BRAUNSTEINER, H., FELLINGER, K., and PAKESCH, F. (1953). Demonstration of a cytoplasmic structure in plasma cells. Blood 8, 916-922. CAJAL, R. Y. (1906). Quelques ant&dent historiques ignores sur les Plasmazellen. Anat. An:. 29, 666-673. COONS, A. H., LEDUC, E. H., and CONNOLY, J. M. (1955). Studies on antibody production. I. A method for the histochemical demonstration of specific antibody and its application to a study of the hyperimmune rabbit. J. Exptl. Med. 102, 49-60. EIIRICH, W. E. (1955). Die cellullren BildungsstStten der AntikGrper. Klin. Wochschr. 33, 315322. EHRICH, W. E., DRABICIN, D. L., and FORMAN, C. (1949). Nucleic acids and the production of antibody by plasma cells. J. Exptl. Med. 96, 157-168. FAGRAEUS, A. (1948). Antibody production in relation to the development of plasma cells. Acta Med. &and., Suppl. 204, 122. FERNANDO, N. V. P., and MOVAT, H. 2. (1963). The fine structure of connective tissue. III. The mast cell. Exptl. and Mol. Pathol. 2, in press. FERNANDO, N. V. P., and MOVAT, H. Z. (1962). The fine structure of connective tissue. IV, The macrophage. To be published. HUEBSCHMANN, P. (1913). Das Verhalten der Plasmazellen in der Milz bei infektiSsen Prozessen. Verhandl. deut. Ges. Pathol. 16, 110-115. LEDUC, E. H., COONS, A. H., and CONNOLLY, J. M. (1955). Studies on antibody production. II. The primary and secondary responses in popliteal lymph node of the rabbit. /. Exptl. Med. 102, 61-72. MELLORS, R. C., HEIMER, R., CORCOS, J,, and KORNGOLD, L. (1959). Cellular origin of rheumatoid factor. J. Exptl. Med. 110, 875-886. MOESCHLIN, S., and DEMIRAL, B. (1952). Antikijrperbildung der Plasmazellen in vitro. Klin. Wochschr. 36, 827-829. MORE, R. H., and MOVAT, H. Z. (1959). Character and significance of the cellular response in the collagen diseases and experimental hypersensitivity. Lab. Invest. 6, 873-889. MOVAT, H. Z. (1956). Experimentelle Studien iiber die allergische Gewebsreaktion. B&r. pathol. Anat. 116, 238-348. MOVAT, H. Z., and FERNANDO, N. V. P. (1962). The fine structure of connective tissue. I. The fibroblast. Exptl. and Mol. Pathol. 1, W-534. MOVAT, H. Z., and WILSON, D. R. (1959). The fine structure of plasma cells in relation to their function. Can. Med. Assoc. J. 61, 154-159. NOSSAL, G. J. V., and LEDERBERG, J, (1958). Antibody production by single cells. Nature 161, 1419-1420. NOSSAL, G. J. V., and MXKELK, 0. (1962). Autoradiographic studies on the immune response. II. The kinetics of plasma cell proliferation. 1. Exptl. Med. 116, 209-230. ORTEGA, L. G., and MELLORS, R. C. (1957). Cellular sites of formation of gamma globulin. J. Exptl. Med. 106, 627-640. PALADE, G. E. (1956). Intracisternal granules in the exocrine cell of the pancreas. J. Biophys. Biochem. Cytol. 2, 417-422. PALAY, S. L. (1958). The morphology of secretion. In “Frontiers in Cytology” (S. L. Palay, ed.), pp. 305-342. Yale Univ. Press, New Haven, Connecticut. PAPPENHEIM, A. (1901). Wie verhalten sich die Unnaschen Plasmazellen zu Lymphocyten? Virrhow’s Arch. pathol. Anat. 166, 424-453.

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PEARSE, A. G. E. (1949). The nature of Russell bodies and Kurloff bodies; observation on the cytochemistry of plasma cells and reticulum cells. J. Clin. Pathol. 2, 81-90. POLICARD, A., and BESSIS, M. (1956). Sur l’espace p6rinucl6aire. Exptl. Cell Research 11, 490-492. REISS, E., MERTENS, E., and EHRICH, W. E. (1950). Agglutination of bacteria by lymphoid cells in vitro. Proc. Sot. Exptl. Biol. Med. 14, 732-735. SJ~STRAND, F. S., and HANSON, V. ( 1954). Ultrastructure of Golgi apparatus of exocrine cells of mouse pancreas. Exptl. Cell. Research 7, 393-414. STOECPENIUS, W. (1957a). Golgi-Apparat und Centriol menschlicher Plasmazellen. Frankfurt Z. Pathol. 68, 404-409. STOECICENIUS, W. (1957b). Weitere Untersuchungen am lymphatischen Gewebe. Verhandl. de&. Ges. Pathol. 41, 304-312. TIII~RT, J. P. (1958). Etude sur le plasmocyte en contraste de phase et en microscopic ClCctronique. Rev. Htmatol. 13, 61-78. TIIIBRY, J. P. (1960). Microcinematographic contributions to the study of p!asma cells. In “Ciba Foundation Symposium on Cellular Aspects of Immunity” (G. E. W. Wolstenholme and M. O’Connor, eds.), J. and A. Churchill, London. Lixx,z, P. G. (1891). iiber Plasmazellen insbesondre beim Lupus. Momtsrhr. prakt. Dermatol. 12, 296.317. UNKA. P. G. (1913). Die Herknuft der Plasmazellen Virchow’s Arch. pathol. dnat. 214, 320-339. Zur submikroskopischen Morphologic von Plasmazellen mit Rus~~ELLEXSIEh, H. J. (1957). selschen KGrperchen und Eiweiskristallen. Beitr. Pathol. Anat. 118, 173-202. WIXSII, R. .4. (1962). Light and electron microscopic correlation of periodic acid-Schiff reaction in the human plasma cell. Am. J. Pathol. 40. 285-296. WHITE. R. G. (1954). Observations on the formation and nature of Russell bodies. Brit. J. Exptl. Pathol. 35, 365-376.