scholarly journals ELECTRON MICROSCOPY OF PLASMA-CELL TUMORS OF THE MOUSE

1961 ◽  
Vol 9 (2) ◽  
pp. 353-368 ◽  
Author(s):  
D. F. Parsons ◽  
E. B. Darden ◽  
D. L. Lindsley ◽  
Guthrie T. Pratt
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Plasma Cell ◽  
Electron Microscope Study ◽  
Plasma Cells ◽  
Granular Body ◽  
Virus Particles ◽  
Cytoplasmic Structure ◽  
Large Numbers ◽  
C3h Mice

An electron microscope study was made of a series of transplanted MPC-1 plasma-cell tumors carried by BALB/c mice. Large numbers of particles similar in morphology to virus particles were present inside the endoplasmic reticulum of tumor plasma cells. Very few particles were seen outside the cells or in ultracentrifuged preparations of the plasma or ascites fluid. In very early tumors particles were occasionally seen free in the cytoplasm adjacent to finely granular material. In general, the distribution of these particles inside endoplasmic reticulum is similar in early and late tumors. A few transplanted X5563 tumors of C3H mice were also examined. Large numbers of particles were found in the region of the Golgi apparatus in late X5663 tumors. A newly described cytoplasmic structure of plasma cells, here called a "granular body," appears to be associated with the formation of the particles. Particles present in MPC-1 tumors are exclusively of a doughnut form, whereas some of those in the inclusions of the late X5563 tumors show a dense center. Normal plasma cells, produced by inoculation of a modified Freund adjuvant into BALB/c mice. have been compared morphologically with tumor plasma cells of both tumor lines.

scholarly journals ELECTRON MICROSCOPY OF PLASMA-CELL TUMORS OF THE MOUSE

1961 ◽  
Vol 9 (2) ◽  
pp. 369-381 ◽  
Author(s):  
D. F. Parsons ◽  
M. A. Bender ◽  
E. B. Darden ◽  
Guthrie T. Pratt ◽  
D. L. Lindsley
Keyword(s):  
Electron Microscopy ◽  
Tissue Culture ◽  
Complex Structure ◽  
Granular Body ◽  
Virus Particles ◽  
Culture Cells ◽  
Large Numbers ◽  
Tumor Agent

The X5563 tumor has been grown in tissue culture. Cells similar to those of the original tumor migrated from the explant and attached to the glass walls of the culture vessels. Electron microscopy showed that large numbers of particles, similar in morphology to virus particles, were associated with these cells after 7 days of culture. The two principal types of particles found in the tumor in vivo appear to be present in vitro. Many more of these particles, however, were larger and showed a more complex structure. Whereas the particles were mainly localized inside endoplasmic reticulum or the Golgi zone in the tumors in vivo, in the tissue culture the majority of the particles were associated with the plasma membrane and were found outside of the cells. The relation of the particles to the granular body is discussed as well as a possible relation to the mammary tumor agent.

scholarly journals Electron Microscopic Localization of Russell Bodies in the Human Plasma Cell

Blood ◽  
1960 ◽  
Vol 16 (3) ◽  
pp. 1307-1312 ◽  
Author(s):  
RONALD A. WELSH
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Human Plasma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Electron Microscopic ◽  
Degenerative Process ◽  
Microscopic Localization ◽  
Electron Microscopic Localization

Abstract The location of Russell bodies in the human plasma cell was shown by electron microscopy to be within the intracisternal space of the endoplasmic reticulum. The significance of this finding was discussed from the standpoint of possible intracellular function of the endoplasmic reticulum. The appearance of the affected plasma cells tended to negate a degenerative process, and the suggestion was offered that the Russell body results from a condensation of intracisternal secretion.

Electron Microscope Study of RNA's of Paramyxoviruses

1972 ◽  
Vol 30 ◽  
pp. 196-197
Author(s):  
Ruchama Baum ◽  
J.T. Seto
Keyword(s):  
Electron Microscopy ◽  
Electron Microscope ◽  
Electron Microscope Study ◽  
Sendai Virus ◽  
Sodium Dodecyl ◽  
Rna Molecules ◽  
Virus Particles ◽  
Molecular Weights ◽  
Length Measurements

The ribonucleic acid (RNA) of paramyxoviruses has been characterized by biochemical and physiochemical methods. However, paramyxovirus RNA molecules have not been studied by electron microscopy. The molecular weights of these single-stranded viral RNA molecules are not known as yet. Since electron microscopy has been found to be useful for the characterization of single-stranded RNA, this investigation was initiated to examine the morphology and length measurements of paramyxovirus RNA's.Sendai virus Z strain and Newcastle disease virus (NDV), Milano strain, were used. For these studies it was necessary to develop a method of extracting RNA molecules from purified virus particles. Highly purified Sendai virus was treated with pronase (300 μg/ml) at 37°C for 30 minutes and the RNA extracted by the sodium dodecyl sulfate (SDS)-phenol procedure.

scholarly journals Demonstration of a Cytoplasmic Structure in Plasma Cells

Blood ◽  
1953 ◽  
Vol 8 (10) ◽  
pp. 916-922 ◽  
Author(s):  
H. BRAUNSTEINER ◽  
K. FELLINGER ◽  
F. PAKESCH
Keyword(s):  
Electron Microscopy ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Filamentous Structure ◽  
Cytoplasmic Structure

Abstract In normal and pathologic plasma cells of the bone marrow, a specific filamentous structure of the cytoplasm has been revealed by electron microscopy. The significance of this structure is briefly discussed.

Activation of the Endoplasmic Reticulum (ER) Unfolded Protein Response (UPR) in Aggressive B-Cell Lymphomas.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2038-2038
Author(s):  
Olga Balague ◽  
Luis Colomo ◽  
Armando Lopez-Guillermo ◽  
Elias Campo ◽  
Antonio Martinez
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factors ◽  
Western Blot ◽  
Er Stress ◽  
B Cell ◽  
Cell Lines ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Lymphoid Tissues ◽  
B Cell Lymphomas

Abstract BACKGROUND The UPR is a prosurvival pathway activated in cells under ER stress induced by the accumulation of unfolded proteins. UPR activation in B cells normally occurs during the differentiation to antibody secreting plasma cells and requires XBP1activation. XBP-1 is a member of the TREB family of transcription factors that exists in the endoplasmic reticulum (ER) as a 33kDa protein, and in the nucleus as an active 50kDa transcription factor. The UPR stimulates two different ER proteins, ATF-6 and Ire-1, to increase XBP-1 transcription and XBP-1 mRNA splicing resulting in the accumulation of the active 50kDa nuclear protein. Moreover XBP1 is a target of proteosome inhibitors and is related to the aggressive behaviour of some carcinomas. The role of the activation of XBP-1 in lymphomas is still unknown. DESIGN: Reactive lymphoid tissues and 25 neoplastic human B-cell lines representing different stages of B-cell development were studied for XBP-1 expression by western blot and XBP-1, PAX-5, Blimp-1/prdm1, MUM-1/IRF-4 and ICSBP1/IRF-8 by immunohistochemistry. XBP-1 activation was assessed in 225 B-cell lymphomas from the archives of the laboratory of pathology by western blot, RT-PCR and immunohistochemistry . To further evaluate whether XBP-1 activation was related to the plasmacytic program or to ER stress signals we analyzed the cell lines by Western blot for XBP-1 and ATF-6 expression. RESULTS We characterize XBP-1 expression in reactive lymphoid tissues, 25 human cell lines and 225 B-cell tumors. In nearly all tonsillar lymphoid cells XBP-1 was detected as a cytoplasmic protein with a paranuclear dot pattern. Nuclear positivity was observed only in scattered centrocytes in the light zone of the germinal centers and in plasma cells, always coexpressed with plasma cell related transcription factors as MUM-1/IRF-4 and Blimp1/prdm1. Active p50XBP-1 was found in 24/25 cell lines by western blot regardless ATF-6 expression and confirmed by immunohistochemistry . Moreover p50XBP1 was found in 27/31(87%) plasmacytomas, 36/64(56%) DLBCL-ABC and in 3/10(30%) DLBCL-GCB and 22/43(51%) plasmablastic lymphomas. Intriguingly, p50XBP1 was detected also in 2/11(18%)BL and 4/25(16%)MCL with blastic features. CONCLUSIONS.XBP-1 is activated in a subset of follicular centre cells committed to plasma cell differentiation and in plasma cells.UPR prosurvival pathways in the neoplastic cell lines are activated independently of the extent of the ATF-6 activation.p50XBP1 is mostly activated in aggressive B-cell lymphomas regardless to the plasmacytic differentiation of the tumours. Thus, p50XBP-1 may be a new molecular target in the treatment of aggressive B-cell malignancies.

scholarly journals The Morphologic Responses of the Lymphoid System to Homografts

Blood ◽  
1964 ◽  
Vol 24 (2) ◽  
pp. 113-133 ◽  
Author(s):  
JANINE ANDŔ-SCHWARTZ
Keyword(s):  
Electron Microscope ◽  
Cellular Response ◽  
Electron Microscope Study ◽  
Plasma Cells ◽  
Transplantation Immunity ◽  
Large Numbers ◽  
Large Round ◽  
Circulating Antibodies ◽  
Fundamental Unity ◽  
Resistant Animal

Abstract An electron microscope study of the morphologic responses of the rabbit lymph node after skin homografting is described. The results demonstate: (a) the appearance of large, round, ribosome-rich cells—hemocytoblasts— during the first set reaction; (b) a striking proliferation of plasma cells during the second set reaction; (c) the absence of hemocytoblasts in the "6-MP tolerant" animals, and (d) large numbers of two types of unusual cells in the "6-MP resistant" animal. The presence of increased numbers of plasma cells in the second set homograft reaction is in agreement with the findings of circulating antibodies in transplantation immunity and indicates the fundamental unity of the dynamics of the cellular response in various immunological phenomena.

scholarly journals AN ELECTRON MICROSCOPE STUDY OF THE ENDOPLASMIC RETICULUM IN NEWT NOTOCHORD CELLS AFTER DISTURBANCE WITH ULTRASONIC TREATMENT AND SUBSEQUENT REGENERATION

1964 ◽  
Vol 20 (1) ◽  
pp. 175-183 ◽  
Author(s):  
G. G. Selman ◽  
A. Jurand
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Electron Microscope ◽  
Light Microscopy ◽  
Ultrasonic Treatment ◽  
Electron Microscope Study ◽  
Triturus Alpestris ◽  
Notochord Cells ◽  
Parallel Arrays ◽  
Subsequent Regeneration

Ultrasonic treatment of the tails of Triturus alpestris tadpoles, at intensities of 8 to 15 watts/cm2, at 1 megacycle/sec., for 5 minutes, disrupted the epidermis and caused pycnosis in individual cells of the muscle and neural tube, but caused no damage to the notochord that could be detected by light microscopy. Electron microscopy showed that this ultrasonic treatment disordered nearly all the endoplasmic reticulum (ER) of the notochord cells into irregularly rounded vesicles, but within 3 hours after treatment some parallel arrays of normal endoplasmic reticulum were seen near, and continuous with, the outer nuclear membrane. In addition, a re-ordering of the previously disordered ER took place throughout the cytoplasm, in some cases. A classification was made of the state of the ER as shown in electron micrographs of material fixed immediately, 3, and 24 hours after treatment. This showed that more than half the total endoplasmic reticulum in notochord cells was normal again by 24 hours after treatment.

scholarly journals Pharmacologic targeting of plasma cell endoplasmic reticulum proteostasis to reduce amyloidogenic light chain secretion

2021 ◽  
Vol 5 (4) ◽  
pp. 1037-1049
Author(s):  
Bibiana Rius ◽  
Jaleh S. Mesgarzadeh ◽  
Isabelle C. Romine ◽  
Ryan J. Paxman ◽  
Jeffery W. Kelly ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
Covalent Modification ◽  
Alternative Mechanism ◽  
Unfolded Protein ◽  
Disulfide Isomerases ◽  
Protein Response ◽  
Protein Disulfide

Abstract Light chain (LC) amyloidosis (AL) involves the toxic aggregation of amyloidogenic immunoglobulin LCs secreted from a clonal expansion of diseased plasma cells. Current AL treatments use chemotherapeutics to ablate the AL plasma cell population. However, no treatments are available that directly reduce the toxic LC aggregation involved in AL pathogenesis. An attractive strategy to reduce toxic LC aggregation in AL involves enhancing endoplasmic reticulum (ER) proteostasis in plasma cells to reduce the secretion and subsequent aggregation of amyloidogenic LCs. Here, we show that the ER proteostasis regulator compound 147 reduces secretion of an amyloidogenic LC as aggregation-prone monomers and dimers in AL patient–derived plasma cells. Compound 147 was established to promote ER proteostasis remodeling by activating the ATF6 unfolded protein response signaling pathway through a mechanism involving covalent modification of ER protein disulfide isomerases (PDIs). However, we show that 147-dependent reductions in amyloidogenic LCs are independent of ATF6 activation. Instead, 147 reduces amyloidogenic LC secretion through the selective, on-target covalent modification of ER proteostasis factors, including PDIs, revealing an alternative mechanism by which this compound can influence ER proteostasis of amyloidogenic proteins. Importantly, compound 147 does not interfere with AL plasma cell toxicity induced by bortezomib, a standard chemotherapeutic used to ablate the underlying diseased plasma cells in AL. This shows that pharmacologic targeting of ER proteostasis through selective covalent modification of ER proteostasis factors is a strategy that can be used in combination with chemotherapeutics to reduce the LC toxicity associated with AL pathogenesis.

scholarly journals STUDIES ON ANTIBODY-PRODUCING CELLS

1970 ◽  
Vol 132 (3) ◽  
pp. 448-474 ◽  
Author(s):  
Fred G. Gudat ◽  
T. N. Harris ◽  
Susanna Harris ◽  
Klaus Hummeler
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Lymph Node ◽  
Blood Cells ◽  
Plasma Cells ◽  
Great Majority ◽  
The Other ◽  
Nuclear Chromatin ◽  
Parallel Orientation ◽  
Transitional Cells

Antibody-bearing cells of spleen and lymph node of the mouse and rabbit detected by rosette formation with the antigenic red blood cells were collected by micropipet and studied by electron microscopy. More than 300 such cells were examined. In the lymph nodes, rosette-forming cells were all in the lymphocytic and plasmacytic categories. In cells of the mouse spleen, macrophages were also found among the RFC, especially in the later days after immunization. The great majority of the RFC, 70–100%, were of the lymphocytic category. These included small, medium, and large lymphocytes with fine gradations of differentiation, and blast forms with little heterochromatin. The endoplasmic reticulum of these cells occurred in short, very narrow pieces, usually in contact with a mitochondrion. The cells of the plasmacytic category also showed fine gradations from plasmablasts to typical mature plasma cells. Plaque-forming cells of mouse and rabbit were also collected by micropipet. Of 162 such cells, fine gradations were also found throughout the lymphocytic and plasmacytic categories, but in this case the great majority were in the plasmacytic group, and more plasma cells showed amorphous nuclear chromatin. Among antibody-forming cells detected by both reactions, some of the more highly differentiated large lymphocytes contained ER which differed from that in the other large lymphocytes in that the channels were slightly and variably distended, with deposition of some precipitate, and with some tendency to a more nearly parallel orientation of the few channels seen. These were considered transitional cells. Of 10 RFC found in mitosis, all were in the lymphocytic category, in various stages of differentiation, the most advanced of which (in 2 of the 10 cells) was that of the transitional lymphocyte described here. Cells producing plaques facilitated by antisera vs. IgG of the mouse or rabbit (7S) showed the same distribution between cell categories and the same fine gradations as the direct (19S) PFC. Cells producing rosettes which were resistant to lysis in the presence of complement, and were thus presumably producing 7S antibody, showed a distribution similar to that found generally with rosette-forming cells, approximately 80–90% in the lymphocytic category.

scholarly journals THE INDUCED DEVELOPMENT AND HISTOGENESIS OF PLASMA CELLS

1931 ◽  
Vol 54 (3) ◽  
pp. 333-347 ◽  
Author(s):  
Franklin R. Miller
Keyword(s):  
Connective Tissue ◽  
Lymph Nodes ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Protein A ◽  
Blood Stream ◽  
Progressive Increase ◽  
Tissue Cell ◽  
Direct Stimulation ◽  
Large Numbers

As result of finding numerous plasma cells in the omenta of rabbits injected with tuberculo-protein, a method to induce the production of large numbers of these cells has been discovered. The tissues in which they were pronouncedly increased were the subserosal connective tissues of the omentum, body wall, and intestinal wall. The precursor of the plasma cells is a primitive connective tissue cell. As this cell develops into the typical Marshalkó plasma cell there is a progressive increase in the basophilia of the cytoplasm, the nucleus becomes eccentric, a condensation of the chromatin occurs near the nuclear membrane, and there is a loss of the nucleoli. At the time when the nucleus assumes the eccentric position, the clear area appears in the center of the cytoplasm. The early cells are capable of reproducing themselves by mitosis, while the typical mature cells divide by amitosis. The mature plasma cells often have muddy, spongy cytoplasm which contains acidophilic or hyaline granules as the cells grow old or begin to degenerate. The cells with granules or hyaline bodies usually have pycnotic or fragmented nuclei. These cells are the final stage reached by some plasma cells. Others, when degenerating, show vacuoles and signs of senility. Those with the granules and hyaline bodies are the so called Russell body cells. Plasma cells developed in greatest numbers after our largest injections of tuberculo-protein. The differentiation into young, mature, and senile forms was most clearly recognizable when some days had been allowed to elapse after the last large injection of the stimulating agent. A description of the plasma cell as viewed supravitally has been given. The cells are met in the blood stream as well as in the tissues. They are characterized by their deep yellowish gray cytoplasm, indistinct eccentrically placed nuclei, and large numbers of mitochondria. The plasma cells differ from lymphocytes, in that they did not develop in large numbers after direct stimulation of the lymph nodes with tuberculo-protein. The young plasma cells also differ in morphology from the young lymphocytes. When plasma cells were found in the lymph nodes they were in the connective tissue cords. The plasma cell is a definite entity, having a maturation cycle. It is stimulated to great proliferation by certain toxic irritants.

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