Showing papers on "Plasma cell published in 1984"
TL;DR: In some patients, antigens normally found at earlier stages of B cell differentiation were expressed by peripheral blood lymphocytes and/or bone marrow plasma cells, and patients that showed such peripheral blood involvement were found to have a larger tumor burden and higherBone marrow plasma cell proliferative activity.
88 citations
Journal Article•
TL;DR: A monoclonal antibody that defines a new and distinct plasma cell antigen, termed PC-1, was developed against human plasmacytoma cells and is useful for the study of the terminal stages of normal B cell differentiation to plasma cells, and may offer insight into the heterogeneity of the plasma cell dyscrasias.
Abstract: A monoclonal antibody that defines a new and distinct plasma cell antigen, termed PC-1, was developed against human plasmacytoma cells This antigen is strongly expressed on normal plasma cells isolated from bone marrow and on abnormal plasma cells isolated from myelomas, plasma cell leukemias, and plasmacytomas The antigen is not detected on normal T or B lymphocytes, granulocytes, or monocytes, and with the exception of plasma cells, is absent on malignancies of B, T, or myeloid origin Utilizing pokeweed mitogen to induce human B lymphocyte differentiation in vitro, PC-1 is expressed when B cell determinants are lost and the plasmacytoid morphology, intracytoplasmic immunoglobulin-staining, and surface PCA-1- and T10-staining characteristic of plasma cells appear This antigen is useful for the study of the terminal stages of normal B cell differentiation to plasma cells, and may offer insight into the heterogeneity of the plasma cell dyscrasias
83 citations
TL;DR: Findings suggest that immune complex-mediated damage does not play a major role in the epithelial damage in inflammatory bowel disease.
69 citations
TL;DR: It is concluded that this antigen is unique among known B cell differentiation antigens in its intermittent pattern of expression during B cell development and well suited for studies of B cell ontogeny.
Abstract: We have examined the expression of a cell surface antigen by B lineage cells in human fetuses, newborns and adults using a newly produced monoclonal antibody, HB-7. The HB-7 antigen was found to be a protease sensitive 45,000 MW molecule that appeared to be the same molecule recognized by the OKT-10 antibody. The HB-7 reactive molecule was expressed by all fetal pre-B and B cells, and 50% of newborn blood and adult bone marrow B cells. In contrast, only a small minority of B cells (2-12%) from blood, spleen and tonsil of adults were weakly HB-7+. The pokeweed mitogen-responsive B cell precursors of plasma cells were also HB-7-, but the HB-7 antigen was re-expressed during the plasma cell stage. We conclude that this antigen is unique among known B cell differentiation antigens in its intermittent pattern of expression during B cell development. The reactivity of the HB-7 antibody with immature, but not mature, B cells makes it well suited for studies of B cell ontogeny.
60 citations
TL;DR: The stage of differentiation at which B-lymphoblastoid cell lines have been arrested can be changed in vitro, and cell-line dependent and inducer-dependent differences in the differentiation response were apparent.
Abstract: N-Butyrate, an effective inducer of synthesis of Epstein-Barr virus (EBV) antigens in virus-producer P3HR-1 cells, has recently been shown (2) to induce morphological differentiation towards plasma cell in nonproducer Raji cells. The effects of n-butyrate and 12-O-tetradecanoylphorbol-13-acetate (TPA) on both EBV-antigen induction and cell differentiation in two virus-nonproducer lymphoblastoid cell lines, Raji and NC37, were now studied. The following observations were made (1). On its own either drug induced 1-2 per cent of cells to EBV-early-antigen positivity in both lines; their mixture induced 35 and 15 per cent positive cells in Raji and NC37 respectively (2). In Raji, n-butyrate induced about 80 per cent of cells to differentiate to plasmablast or plasma cell morphology, whereas TPA only induced the early stages of differentiation in 8 per cent of cells; a mixture of both inducers produced a similar effect as TPA alone. The addition of TPA alone or butyrate-TPA mixture led to some cellular alterations resembling virus-specific changes in virus-producer cell lines. In NC37, either drug alone or their mixture drove 13 per cent of cells to differentiate into plasmablasts or earlier stages of differentiation. In the presence of TPA protrusions and "loops" were seen on cell surfaces. Evidently, the stage of differentiation at which B-lymphoblastoid cell lines have been arrested can be changed in vitro. However, cell-line dependent and inducer-dependent differences in the differentiation response were apparent.
38 citations
TL;DR: Investigation of a mesenteric mass found in an 18-yr-old man with at least 11 yr of growth retardation and anemia found histologic features of the hyaline vascular and plasma cell types of Castleman's disease with multinucleate giant cells probably of macrophage origin suggest that giant lymph node hyperplasia is a local inflammatory reaction.
37 citations
TL;DR: The increases in IgA and IgM plasma cells suggest that the deposits of extracellular IgAand IgM observed in coeliac mucosa are locally produced, and the increase in IgE plasma cells raises the possibility that reaginic type hypersensitivity may be involved in coeeliac disease.
Abstract: Using a modified immunoperoxidase technique to achieve optimum staining and reproducible counts of plasma cells in paraffin embedded tissue, IgA, IgM, IgE, and IgG plasma cells were studied in small bowel biopsies from 20 controls, 23 untreated coeliac patients, 19 treated coeliac patients, and seven patients with Crohn's disease not involving duodenum or jejunum. In controls the ratio of the mean counts for IgA, IgM, IgE, and IgG plasma cells was 2.5:1:1:1 respectively. In patients with untreated coeliac disease, counts of all types of plasma cell were significantly increased approximately two-fold compared with controls although for IgG cells there was considerable overlap. The ratio of the mean plasma cell counts in the untreated coeliac patients was 3.5:1.5:2:1. Counts fell significantly after treatment with a gluten-free diet. There was no significant difference between counts in the controls and the Crohn's disease patients. The changes found in coeliac disease may simply be a non-specific response to mucosal damage. The increases in IgA and IgM plasma cells, however, suggest that the deposits of extracellular IgA and IgM observed in coeliac mucosa are locally produced, and the increase in IgE plasma cells raises the possibility that reaginic type hypersensitivity may be involved in coeliac disease.
37 citations
TL;DR: The results indicate that, in pre-B cells, but not in plasma cells, there must be a mechanism that neutralizes the toxic effect of free H chain.
Abstract: A plasma cell hybridoma frequently loses its immunoglobulin heavy (H) chain spontaneously but rarely is production of its light (L) chain lost. Upon fusion to a pre-B-cell hybridoma that produces no Ig chain, the L chain is frequently lost. In cells without the L chain the H chain, which is derived from the plasma cell, is not chemically modified. Our results indicate that, in pre-B cells, but not in plasma cells, there must be a mechanism that neutralizes the toxic effect of free H chain.
34 citations
Journal Article•
TL;DR: The respiratory tract of sheep is qualitatively similar to the intestine with respect to immunoglobulin synthesis in that the bulk of IgA is locally derived and a smaller but significant local contribution of IgG1 and IgG2 occurs, but that it is a poor source of IgC cell precursors.
Abstract: The amounts of immunoglobulins formed in the respiratory tract of sheep were investigated by comparing the distribution of radiolabelled immunoglobulin between plasma and lymph from the caudal mediastinal lymph node efferent duct which drains 50-70% of lung lymph. In addition, immunoglobulin-containing cells in the lymph node lymph and in the respiratory mucosa were counted by immunofluorescence. Whereas 91.6 +/- 5.92% and 67.73 +/- 10.07% of IgG1 and IgG2 respectively were plasma-derived, only 35.89 +/- 7.09% of IgA was plasma-derived. IgM and albumin were wholly plasma-derived. There was no evidence for selective transport of any immunoglobulins from plasma into lymph. It was estimated that mediastinal lymph node lymph contributed 0.12 g IgA to the circulation daily, the bulk of this being of local origin. There were only few cells expressing IgA in the caudal mediastinal lymph node and its efferent lymph indicating that, unlike gut-associated lymphoid tissue, bronchus-associated lymphoid tissue in sheep is not a major site of IgA cell precursor production. Despite this finding, IgA was the most frequent isotype of Ig-expressing cells in the respiratory mucosa and it is concluded that the locally formed IgA in lymph node lymph originated from mucosal plasma cells. IgM- and IgG-expressing cells were much less numerous than IgA-cells in the mucosa, but were the predominant isotype in the caudal mediastinal lymph node and regional lymph nodes and in mediastinal lymph node efferent lymph. These experiments have established that the respiratory tract of sheep is qualitatively similar to the intestine with respect to immunoglobulin synthesis in that the bulk of IgA is locally derived and a smaller but significant local contribution of IgG1 and IgG2 occurs, but that it is a poor source of IgA cell precursors. This implies that the IgA plasma cell population in the respiratory mucosa probably originates from distant mucosal sites.
29 citations
TL;DR: Immunologic studies of the mass showed that the B lymphocytes were polyclonal and the T lymphocyte helper/suppressor cell ratio was normal, suggesting that giant lymph node hyperplasia is a local inflammatory reaction.
23 citations
TL;DR: The abnormal DNA content of bone marrow plasma cells was not correlated with any clinical and laboratory characteristic and it affected neither response to therapy nor survival in patients studied at diagnosis.
TL;DR: CMV could be responsible for abnormal B-cell proliferation in patients with defective immunoregulation who receive immunotherapy, as in lymphoid abnormalities associated with Epstein-Barr virus.
Abstract: A male infant in whom multiple recurrent multiorgan infections developed during the first six months of life was found to have combined immunodeficiency. Progressive pulmonary disease developed at age two years; cytomegalovirus (CMV) was isolated from the respiratory tract and urine. Three separate intramuscular grafts of cultured thymus fragments did not produce change in the course of the illness. Soon after age three years, IgG lambda appeared in the serum as an M-component. The patient died at age three and one-half years, with respiratory insufficiency due to pulmonary fibrosis. At autopsy, a malignant plasma cell infiltrate was limited to the retroperitoneum. The infiltrate replaced lymph node structures and surrounded nerve fascicles, which appeared necrotic, and contained CMV inclusions in ganglion cell nuclei. The plasma cells showed strong monoclonal staining for IgG lambda. Also noted was positive staining for J-chain, which has been reported previously in malignant plasma cells producing IgG. CMV could be responsible for abnormal B-cell proliferation in patients with defective immunoregulation who receive immunotherapy, as in lymphoid abnormalities associated with Epstein-Barr virus.
TL;DR: Plasma cell iron was found in patients without other morphologic changes of alcoholism such as megaloblastosis, erythroid vacuolization, and ringed sideroblasts and could be demonstrated in biopsy and autopsy material from extra-marrow sites.
Abstract: In order to identify the major clinical features and laboratory findings in patients with plasma cell iron, the authors reviewed the medical records and marrow aspirates of 53 consecutive patients with plasma cell iron hospitalized at Nashville Veterans Administration Hospital over a seven-year period. Plasma cell iron was associated most commonly with alcoholism and occurred in marrows with increased, normal, and decreased iron stores. In patients with decreased marrow iron, plasma cells were the major site of stainable iron. Plasma cell iron was found in patients without other morphologic changes of alcoholism such as megaloblastosis, erythroid vacuolization, and ringed sideroblasts. Plasma cell iron could be demonstrated in biopsy and autopsy material from extra-marrow sites. Ultrastructural studies showed iron always was located in membrane bound lysosomal vesicles of plasma cells.
TL;DR: About 19% of apparently nonatypical lymphocytes in the biopsy material of this case were found to have ribosome-lamella complexes (RLC) similar to those previously described in patients with hairy cell leukemia and some other hematologic disorders.
Abstract: A case of lymphoid hyperplasia with prominent plasmacytic proliferation histologically and with polyclonal hypergammaglobulinemia and anemia clinically was reported. This condition in a 54-year-old Japanese male was probably a type of plasma cell dyscrasia similar to a plasma cell variant of Castleman's disease. About 19% of apparently nonatypical lymphocytes in the biopsy material of this case were found to have ribosome-lamella complexes (RLC) similar to those previously described in patients with hairy cell leukemia and some other hematologic disorders. An intimate association with the rough endoplasmic reticulum of these structures suggested aberrant protein synthesis by B-lymphocytes.
TL;DR: The first reported osteosclerotic plasmacytoma of the maxillary bone and orbital floor is described, which is a rare variant of plasma cell tumors which usually produce osteolytic lesions rather than bony sclerosis.
Abstract: Plasma cell neoplasms have been classified as multiple myeloma, solitary plasmacytoma and extramedullary plasmacytoma. They are usually considered as osteolytic lesions of bone except for the rare occurrence of osteosclerotic lesions. This paper describes the first reported osteosclerotic plasmacytoma of the maxillary bone and orbital floor. The difficulties in establishing a diagnosis and the relationship to other plasma cell neoplasms are discussed.Osteosclerotic plasmacytomas are a rare variant of plasma cell tumors which usually produce osteolytic lesions rather than bony sclerosis. Sixty-eight patients with the osteosclerotic variant have appeared in the world literature, with an overall incidence of about 1 per cent in a large series of plasma cell neoplasms (Dreidger and Pruzanski, 1979). There have been only six previous cases of solitary osteosclerotic plasmacytomas reported (Morley and Schweiger, 1964; Roberts et al., 1974; Rodriguez et al. 1976; Rushton, 1965; Schneinker, 1938; Brigham Medical Review, 1961) involving spine, sternum, or rib. None have previously been reported in the head and neck area.Plasma cell tumors have been classified into multiple myeloma, solitary plasmacytomas of bone, and extramedullary plasmacytomas. Multiple myeloma is a disseminated plasma cell
malignancy characterized by the production of homogeneous immunoglobulins (whole or fragments) which appear in the serum and urine. Plasma cell tumors can also occur as solitary plasmacytomas, usually in bone, but also in soft tissue. With time, most solitary plasmacytomas develop disseminated disease with all the characteristics of multiple myeloma (Wiltshaw, 1976). Extramedullary plasmacytomas arise in soft tissue rather than bone, and primarily occur in the head and neck region. Clinically, they remain localized and less frequently develop into disseminated myeloma.
01 Jan 1984
TL;DR: B lymphocytes derive from bone marrow pluripotent stem cells and mature through a number of discernible stages, but studies of B cell maturation and differentiation based solely on Ig expression lack detail, and additional markers are needed to allow a clearer understanding of the entire B cell lineage.
Abstract: B lymphocytes derive from bone marrow pluripotent stem cells and mature through a number of discernible stages. Antigen stimulates B cells to differentiate either into memory cells or into antibody-producing plasma cells. Distinct stages of B cell maturation can be recognised by the expression of immunoglobulin (Ig), which is the characteristic functional product of B lymphocytes. However, studies of B cell maturation and differentiation based solely on Ig expression lack detail, and additional markers are needed to allow a clearer understanding of the entire B cell lineage.
TL;DR: Evidence is presented that the light-microscopically identified mature plasma cell is not the main antibody-forming cell and does not show 3H-Thymidine incorporation and should be considered as a non-dividing end-cell.
Journal Article•
TL;DR: The large number of plasma cells present in the lesions suggests an immunological basis for the condition and suggests a seasonal occurrence of the condition.
Abstract: Plasma cell pododermatitis, an uncommon disease of unknown etiology, is described in a six year old male domestic short-haired cat. The cat was referred with a history of lameness associated with swelling, softness and ulceration of the foot pads. The history suggested a seasonal occurrence of the condition. The dermis and subcutis of the foot pads were infiltrated by inflammatory cells which were mainly plasma cells. The large number of plasma cells present in the lesions suggests an immunological basis for the condition.
TL;DR: A 45-year-old-woman with plasma cell leukemia and mild renal insufficiency is added to the list of plasma cell dyscrasias associated with κ- and/or λ-chain nephropathy.
Abstract: A 45-year-old-woman had plasma cell leukemia (PCL) and mild renal insufficiency. Renal biopsy findings were compatible with kappa-chain nephropathy. Our case adds PCL to the list of plasma cell dyscrasias associated with kappa- and/or lambda-chain nephropathy.
TL;DR: Lymph node and spleen responses in infected animals paralleled the proliferation of the amebic liver abscess, and lymphocyte repopulation was noted in the PCA and PAA; germinal centers were depleted of blast cells and the spleen red pulp had contracted.
Abstract: Antibody responses and histological changes in hepatic lymph nodes and spleen of gerbils (Meriones unguiculatus) during the course of experimental hepatic amebiasis (5–60 days), or in those injected with extracts ofEntamoeba histolytica, are described. Lymph node and spleen responses in infected animals paralleled the proliferation of the amebic liver abscess. However, spleen follicle responses were similar in animals that received low or high doses of the amebic extract and differed histologically from those with amebic liver abscess. Liver abscesses, up to 30 days postinfection (pi), doubled in weight between 10 and 15 and between 20 and 30 days pi. Early changes (10 days pi) in the lymphoreticular tissues were characterized by increased size and weight of the organs, hyperplastic follicles, and blastogenesis in the T-dependent areas. At 20 and 30 days pi, the size of spleen follicles increased and there was depletion of lymphocytes from the periarterial area (PAA), as well as gross extension of the red pulp, accompanied by extramedullary erythropoiesis and megakaryocytosis. The paracortical areas (PCA) of lymph nodes were depleted of lymphocytes and histocytosis throughout the organ, and there was intense plasma cell activity in the medulla. At 60 days pi, lymphocyte repopulation was noted in the PCA and PAA; germinal centers were depleted of blast cells and the spleen red pulp had contracted. Antiamebic antibody titers were low throughout the infection. Changes in the cellularity of the lymphoid organs are discussed in relation to the proliferation of the amebic liver abscesses in infected animals and in those which were injected with the amebic extract.
TL;DR: Acid hydrolases--some of which showing plasma cell type of activity--are expressed during B-CLL cells differentiation induced in vitro, and this results confirm the value of cytochemistry in subtyping B-cell malignancies.
TL;DR: Kohler and Milsteins' technique of monoclonal antibody production is now being exploited in most areas of biology, to immortalize and then select for clones of plasma cells secreting antibody against a desired antigen.
Abstract: Kohler and Milsteins' (1) technique of monoclonal antibody production is now being exploited in most areas of biology The essence of the method is to immortalize and then select for clones of plasma cells secreting antibody against a desired antigen Individual plasma cells secrete antibody of a single antigenic specificity and monoclonal antibodies are thus obtainable from a cell line derived from a single plasma cell Once established, clonal lines of hybridomas (hybrids composed of plasma cells fused with immortal myeloma cells) provide an infinite supply of antibodies with reproducible properties Monoclonal antibodies may be produced without extensive purification of the immunogen, and without the tedious cross-adsorption steps often necessary for production of specific antisera So far, only mouse and rat hybridomas are being produced routinely, while human monoclonal antibodies of potential therapeutic value are technically more difficult to obtain
TL;DR: The plasma cell infiltrate of the small intestine in alpha‐chain disease has been studied ultrastructurally in an attempt to determine whether there is a significant nuclear‐cytoplasmic asychrony that could be used as evidence for the neoplastic nature of the disease, even in its early stages.
Abstract: The plasma cell infiltrate of the small intestine in alpha-chain disease has been studied ultrastructurally in an attempt to determine whether there is a significant nuclear-cytoplasmic asynchrony that could be used as evidence for the neoplastic nature of the disease, even in its early stages. No such asynchrony was identified. In the early stages of the disease, the infiltrate was mainly of slightly immature plasma cells indistinguishable from those of coeliac disease. Later stages were marked by the presence of less differentiated immunoblastic cells arising in the deep mucosa and infiltrating into glands. Multinucleate plasmacytoid cells were thought to be degenerate cells. The significance of these findings is discussed in relation to the nature of alpha-chain disease and immunoproliferative small intestinal disease in general.
TL;DR: Six cases are reported of a previously undescribed unusual composite variant of lymphoplasmacytic lymphoma that is not readily classifiable by either the Rappaport or the Lukes and Collins classifications, or by the recently proposed Working Formulation.
Abstract: Six cases are reported of a previously undescribed unusual composite variant of lymphoplasmacytic lymphoma that is not readily classifiable by either the Rappaport or the Lukes and Collins classifications, or by the recently proposed Working Formulation. These cases are characterized by a partly nodular, partly diffuse proliferation of lymphoid cells surrounded by a separate, zonally distinct proliferation of large plasmacytoid cells. The latter cells are located in medullary and paracortical areas in lymph nodes and in the marginal zone of the white pulp and in the red pulp in the spleen. This distinct zonal characteristic was noted in the small bowel as well in one case. Five of our six patients were male, and their ages ranged from 46 to 68 years. Three had a monoclonal serum IgM and one had hyperglobulinemia that was not further characterized. Three had evidence of an altered immune state. In all cases, monoclonal IgM was demonstrated in involved tissues by an immunoperoxidase technique. These cases are unusual because of the unique topographic segregation of the varying types of tumor cells in all cases, and because of the association of paraproteinemia with nodular lymphoma in three. The resemblance of this tumor to the plasma cell variant of giant lymph node hyperplasia with which two cases were originally confused, and to lymph nodes in patients with autoimmune diseases, may be responsible for its lack of recognition. Cancer 53:1103-1108, 1984.
TL;DR: It is concluded that polyclonal Ig evaluation appeared to be of diagnostic and prognostic values in the management of malignant PCD.
Abstract: Polyclonal immunoglobulins (Ig) were measured at diagnosis and/or following chemotherapy in 226 patients with a malignant plasma cell dyscrasia (PCD), including 11 patients with solitary myeloma (SM) and 215 patients with multiple myeloma (MM). At diagnosis, Ig synthesis suppression was observed in 80.7% of patients with MM but never in case of SM (p less than 0.001). In patients with MM, there was a clear correlation between IgA or IgM levels (but not IgG) and the total body burden of myeloma cells (p less than 0.01), the lowest levels being observed in patients presenting with the highest myeloma cell mass. Of major interest, for patients evaluated following the induction of chemotherapy, an increase of Ig, from low to normal levels, was only noted in case with a myeloma cell mass regression over 90% and successful achievement of a greater than or equal to 1-year plateau period. We concluded that polyclonal Ig evaluation appeared to be of diagnostic and prognostic values in the management of malignant PCD.
01 Jan 1984
TL;DR: The present studies were initiated to learn about quantitative and qualitative changes of surface structures during B lymphocyte differentiation and plasma cell formation
Abstract: The events leading to the stimulation of B lymphocytes are not yet well characterized. In addition to the specific role of surface immunoglobulin, a variety of receptors and antigenic molecules, of cellular interactions, and of proteolytic reactions has been recognized to participate in the regulation of B lymphocyte activity. The present studies were initiated to learn about quantitative and qualitative changes of surface structures during B lymphocyte differentiation and plasma cell formation.
TL;DR: An analysis was performed according to different cytoarchitectural forms of the endoplasmic reticulum (ER) and it was found that an ultrastructurally distinct type of plasma cell was enriched 3.5-fold over the original sample by the separation procedure.
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01 Jan 1984
TL;DR: The light microscopy examination of the plasma cells is usually sufficient to establish the diagnosis but, in some cases, the distinction between leukemic myelomatosis and chronic lymphocytic leukemia is rather difficult, and the use of electron microscopy is necessary to achieve the right decision.
Abstract: Plasma cell leukemia (PCL) is an infrequent condition that accounts for less than 2% of the plasmacytic dyscrasias [1]. It may appear as a terminal phase of the classical form of multiple myeloma, or as an acute leukemic condition, clinically identical with other forms of acute leukemia [2]. The diagnosis is based on the presence of plasma cells in the peripheral blood, which may exceed 50% of the total white blood cell count, and may be presented at different stages of maturation, from immature plasmablasts to mature plasmacytes. The light microscopy examination of the plasma cells is usually sufficient to establish the diagnosis but, in some cases, the distinction between leukemic myelomatosis and chronic lymphocytic leukemia is rather difficult [3, 4], and the use of electron microscopy is necessary to achieve the right decision.
Journal Article•
01 Jan 1984
TL;DR: This chapter shall focus on studies of leukaemic B and T lymphocytes which were directed towards defining the molecular events and cellular interactions that control immunoglobulin synthesis, and on malignancies of T cell origin which are of exceptional interest.
Abstract: A series of cells and antibody proteins make up a critically important system of immunity. This immunological system, when functioning adequately, protects us against infections by bacterial, parasitic, viral and fungal agents, and even against the growth of cancer cells. When the system does not function normally, we are plagued by a wide array of diseases. One of the fundamental questions in the field of immunology is how the immune system recognises up to 100 million substances as foreign, yet normally does not direct its attack against the tissues of the individual. Over the past few years there have been enormous advances in our understanding of how the human immune system is regulated. A number of these insights have emerged from the study of neoplasms of the B cell/plasma cell and of the T cell series. For example, the recognition that paraproteins derived from patients with multiple myeloma, represent homogeneous unmunoglobulins was an indispensable step in understanding the structural and functional aspects of immunoglobulin molecules. In this chapter I shall focus on studies of leukaemic B and T lymphocytes which were directed towards defining the molecular events and cellular interactions that control immunoglobulin synthesis. In the first section I shall discuss studies applying the techniques of molecular biology to lymphoid cells which were directed towards defining the early events in the differentiation of stem cells into B cells. In the second section I shall consider the terminal maturation of B cells into immunoglobulin-synthesising plasma cells. Here I shall focus on malignancies of T cell origin which are of exceptional interest because in certain cases they retain immunoregulatory properties and are useful in resolving questions concerning the regulatory network of cells that control B cell maturation and immunoglobulin production. In the final section I shall consider the physiological and pathophysiological factors that control the metabolism of immunoglobulin molecules and the abnormalities in immunoglobulin survival that lead to disorders of immunoglobulin levels in disease states.