Showing papers on "Plasma cell published in 1995"
TL;DR: Using the lymphocytic choriomeningitis virus (LCMV) model, it is found that after resolution of the acute infection, a population of virus-specific plasma cells appears in the bone marrow and constitutes the major source of long-term antibody production.
Abstract: Antiviral antibody production is often sustained for long periods after resolution of an acute viral infection. Despite extensive documentation of this phenomenon, the mechanisms involved in maintaining long-term antibody production remain poorly defined. As a first step towards understanding the nature of long-term humoral immunity, we examined the anatomical location of antibody-producing cells during acute viral infection. Using the lymphocytic choriomeningitis virus (LCMV) model, we found that after resolution of the acute infection, when antiviral plasma cells in the spleen decline, a population of virus-specific plasma cells appears in the bone marrow and constitutes the major source of long-term antibody production. Following infection of adult mice, LCMV-specific antibody-secreting cells (ASC) peaked in the spleen at 8 days postinfection but were undetectable in the bone marrow at that time. The infection was essentially cleared by 15 days, and the ASC numbers in the spleen rapidly declined while an increasing population of LCMV-specific ASC began to appear in the bone marrow. Compared with the peak response at 8 days postinfection, time points from 30 days to more than 1 year later demonstrated greater-than-10-fold reductions in splenic ASC. In contrast, LCMV-specific plasma cell numbers in the bone marrow remained high and correlated with the high levels of antiviral serum antibody. The presence of LCMV-specific plasma cells in the bone marrow was not due to persistent infection at this site, since the virus was cleared from both the spleen and bone marrow with similar kinetics as determined by infectivity and PCR assays. The immunoglobulin G subclass profile of antibody-secreting cells derived from bone marrow and the spleen correlated with the immunoglobulin G subclass distribution of LCMV-specific antibody in the serum. Upon rechallenge with LCMV, the spleen exhibited a substantial increase in virus-specific plasma cell numbers during the early phase of the secondary response, followed by an equally sharp decline. Bone marrow ASC populations and LCMV-specific antibody levels in the serum did not change during the early phase of the reinfection, but both increased about two-fold by 15 days postchallenge. After both primary and secondary viral infections, LCMV-specific plasma cells were maintained in the bone marrow, showing that the bone marrow is a major site of long-term antibody production after acute viral infection. These results documenting long-term persistence of plasma cells in the bone marrow suggest a reexamination of our current notions regarding the half-life of plasma cells.
384 citations
TL;DR: The essential role of IL-6 in the development of B lineage tumors in vivo is defined and experimental support for continued efforts to modulate this cytokine in the treatment of appropriate human B cell malignancies is provided.
Abstract: Interleukin (IL) 6 has been suggested to be the major cytokine responsible for proliferation of neoplastic plasma cells in both human myeloma and mouse plasmacytoma. Much of the evidence supporting this suggestion is derived from in vitro studies in which the survival or proliferation of some plasma cell tumors has been found to be IL-6 dependent. However, it remains unclear whether this dependency is the consequence of in vivo or in vitro selective pressures that preferentially expand IL-6-responsive tumor cells, or whether it reflects a critical in vivo role for IL-6 in plasma cell neoplasia. To address this question, we have attempted to induce plasma cell tumors in normal mice and in IL-6-deficient mice generated by introduction of a germline-encoded null mutation in the IL-6 gene. The results demonstrate that mice homozygous (+/+) or heterozygous (+/-) for the wild-type IL-6 allele yield the expected incidences of plasma cell tumors. In contrast, mice homozygous for the IL-6-null allele (-/-) are completely resistant to plasma cell tumor development. These studies define the essential role of IL-6 in the development of B lineage tumors in vivo and provide experimental support for continued efforts to modulate this cytokine in the treatment of appropriate human B cell malignancies.
229 citations
TL;DR: It is concluded that monoclonal B cells in the blood of myeloma patient populations include drug-resistant reservoirs of clonotypic cells that may underlie relapse.
167 citations
TL;DR: A new anti-CD79a monoclonal antibody, JCB117, is described, which reacts with human B cells in paraffin embedded tissue sections, including decalcified bone marrow trephines, and is of interest that the antibody labels precursor B-cell acute lymphoblastic leukemia samples, making it the most reliable B- cell marker detectable inParaffin-embedded specimens in this disorder.
158 citations
TL;DR: Analysis of CD45 isoform expression on CD19+ cells in the blood and BM of myeloma patients indicates a heterogeneous continuously differentiating B lineage in contrast to other Bcell malignancies such as B-cell chronic lymphocytic leukemia (B-CLL), lymphoma, or hairy cell le~kemia.
144 citations
Journal Article•
TL;DR: It is shown that significant changes of PC phenotype were associated with malignancy, were correlated with the disease evolution, and could be of diagnostic and prognostic value in individuals with monoclonal gammopathy and patients with multiple myeloma.
Abstract: In order to evaluate putative changes of major adhesion molecule expression on plasma cells (PCs) associated with malignant transformation, tumor spreading, and immortalization, we have quantified and compared the expression of CD56, CD44, CD11a, CD49e, and CD45 RO/RA on normal PCs, malignant PCs from multiple myeloma patients in chronic phase, in accelerated phase with or without extramedullary progression, and from human myeloma cell lines. Plasma cell phenotype was defined with the use of two-color immunofluorescence in combination with B-B4 or anti-CD38 antibodies. We found that all the adhesion antigens were expressed on normal PCs. Malignancy was characterized by an overexpression of CD56, whereas extramedullary spreading was associated with a dramatic down expression of CD56. Although CD44 remained unchanged, the subpopulation of PCs expressing CD11a, CD49e, and CD45RA/RO were significantly reduced during malignancy, and each of these negative subpopulations increased during disease acceleration. We demonstrated that CD11a and CD49e expression were correlated and defined the same subpopulation of PCs. The phenotype of HMCLs was similar to the expression profile of patients in accelerated phase with extramedullary spreading. In conclusion, we show that significant changes of PC phenotype were associated with malignancy, were correlated with the disease evolution, and could be of diagnostic and prognostic value in individuals with monoclonal gammopathy and patients with multiple myeloma.
144 citations
TL;DR: While angiogenesis was very low or absent in patients with MGUS and non‐active MM, it increased markedly in those with active MM, and the highest detectability of plasma cell adhesion molecules, except LAM‐1, was also found in these patients.
Abstract: Bone marrow plasma cells and stromal cells in multiple myeloma (MM) have been shown to be capable of releasing cytokines with angiogenic properties. Plasma cells can also express adhesion molecules controlling their adhesive interactions with endothelial cells. In the present study, we have evaluated by immunohistochemistry the extent of angiogenesis in the bone marrow of: a) 51 patients with active and non-active MM; b) 25 patients with monoclonal gammopathy of undetermined significance (MGUS). Plasma cells were investigated by flow cytometry for the expression of the adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. The results showed that, while angiogenesis was very low or absent in patients with MGUS and non-active MM, it increased markedly in those with active MM. The highest detectability of plasma cell adhesion molecules, except LAM-1, was also found in these patients. The functional significance of these findings is unknown. Their consistent occurrence in the bone marrow of active myeloma patients, however, strongly suggests that more frequent adhesive interactions between plasma cells and their microvasculature underlie tumor dissemination.
128 citations
TL;DR: RA as well as normal synoviocytes were more potent than other adherent cell lines to support terminal B cell differentiation and should permit the identification of molecules involved in the maturation of B cells into plasma cells, and in their accumulation in rheumatoid synovium.
Abstract: To understand the accumulation of plasma cells within RA synovium, the ability of rheumatoid synoviocytes to support the differentiation of B cells into plasma cells was explored. Tonsillar B lymphocytes cultured over confluent monolayers of synoviocytes, secreted threefold more Igs (mainly IgM) than B cells cultured directly on plastic well. More importantly, synoviocytes enhanced by 14-fold the production of Igs (mainly IgG) by B cells costimulated with Staphylococcus aureus Cowan (SAC) particles. IL-10 and, in a lower extent, IL-2 increased Ig secretion in cocultures, and their combination was synergistic. In the presence of SAC, IL-2, and IL-10, synoviocytes increased by 13-884-fold the production of IgG, which reached 0.19 ng/cell per day. RA as well as normal synoviocytes were more potent than other adherent cell lines to support terminal B cell differentiation. Synoviocyte activity involved both a support of B cell survival, and an induction of the terminal differentiation of B cells into mature plasma cells with typical morphology, high levels of intracytoplasmic Igs, and CD20- CD38high surface expression. The present observation should permit the identification of molecules involved in the maturation of B cells into plasma cells, and in their accumulation in rheumatoid synovium.
127 citations
TL;DR: Bone marrow angiogenesis was observed in patients with active multiple myeloma (MM) and with monoclonal gammopathies of undetermined significance (MGUS) as mentioned in this paper.
Abstract: Angiogenesis is a necessary step in solid tumor progression (growth, invasion and metastasis) with which it correlates and is indicative of an unfavourable prognosis. We observed bone marrow angiogenesis in patients with active multiple myeloma (MM), though not in patients with non-active MM nor with monoclonal gammopathies of undetermined significance (MGUS). Microvessel density increased in parallel with the labeling index (LI%)--an indicator of plasma cell proliferating activity that correlates with prognosis--and defined a risk of MM progression in much the same way as LI% itself. Consequently, bone marrow angiogenesis could be an indication for unfavourable prognosis in MGUS and MM. Angiogenesis has also been demonstrated in lymph nodes involved by B cell non Hodgkin's lymphoma (B-NHL) belonging to the Working Formulation intermediate-grade (diffuse subtypes), and high-grade categories, but not in the low-grade and intermediate-grade (follicular subtype) categories. It correlated with the B-NHL cell proliferating activity, since large increments in this activity have already been demonstrated in intermediate- and high-grade vs low-grade tumors. Active MM, intermediate-grade, diffuse subtypes, and high-grade B-NHLs correspond to the vascular phases of B cell lymphoproliferative diseases, and could thus be assimilated to locally invasive and metastatic solid tumors. Similarly to solid tumors during these stages of progression, tumor B cells are also capable of inducing angiogenesis, both directly and indirectly by activating the inflammation infiltrate--a possibility that was first demonstrated by means of B-NHL implants onto the chick embryo chorioallantoic membrane. Anti-angiogenic therapy can be envisaged as a possible future development.
109 citations
TL;DR: Data show that IL-10 is an IL-6-unrelated growth factor for malignant plasmablastic cells and could be involved in the late phase of MM in vivo.
102 citations
TL;DR: The increased binding of the 64-kDa protein may lead to a generalized increase in polyadenylation efficiency in plasma cells versus early or memory B cells which may be responsible for the increased use of the secretory poly(A) site seen in vivo.
Abstract: During the development of mouse B cells there is a regulated shift from the production of membrane to the secretion-specific forms of immunoglobulin (Ig) mRNA, which predominate in the late-stage or plasma B cells. By DNA transfection experiments we have previously shown that there is an increase in polyadenylation efficiency accompanying the shift to secretion-specific forms of Ig mRNA (C. R. Lassman, S. Matis, B. L. Hall, D. L. Toppmeyer, and C. Milcarek, J. Immunol. 148:1251-1260, 1992). When we look in vitro at nuclear extracts prepared from early or memory versus late-stage or plasma B cells, we see cell stage-specific differences in the proteins which are UV cross-linked to the input RNAs. We have characterized one of these proteins as the 64-kDa subunit of the general polyadenylation factor cleavage-stimulatory factor (CstF) by immunoprecipitation of UV-cross-linked material. The amount of 64-kDa protein and its mobility on two-dimensional gels do not vary between the B-cell stages. However, the activity of binding of the protein to both Ig and non-Ig substrates increases four- to eightfold in the late-stage or plasma cell lines relative to the binding seen in the early or memory B-cell lines. Therefore, the binding activity of a constitutive factor required for polyadenylation is altered in a B-cell-specific fashion. The increased binding of the 64-kDa protein may lead to a generalized increase in polyadenylation efficiency in plasma cells versus early or memory B cells which may be responsible for the increased use of the secretory poly(A) site seen in vivo.
TL;DR: It is shown that Fas expression in myeloma cell lines and CD38hiCD45neg-int patient plasma cells is variable and may reflect a variance in the maturation status of the various plasma cell populations, which may be influenced, in part, by the presence of a soluble protective factor.
TL;DR: The messenger (m) RNA expression of VPF/VEGF and its recep tors in nasal polyp tissues, which is an example of chronic inflammation with remarkable edema, suggested that plasma cells may play an important role in the development of edema in chronic inflammation through the production ofVPF /VEGF.
Abstract: Edema occurs in some types of chronic inflammation such as nasal polyps, uterine cervical polyps and gastric hyper-plastic polyps. However, the factors or cellular components involved in the development of edema in chronic inflammation remain to be clarified. Recently, the gene encoding vascular permeability factor (VPF) or vascular endothelial growth factor (VEGF) and the genes encoding its receptors (kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1 [fit-1]) have been cloned. VPF/VEGF induces vascular hyperpermeability and vascular endothe lial proliferation through KDR or fit-1 receptors. As there is a possibility that VPF/VEGF may play a role in the development of edema in chronic inflammation, we examined the messenger (m) RNA expression of VPF/VEGF and its recep tors in nasal polyp tissues, which is an example of chronic inflammation with remarkable edema. Using northern blotting, all nasal polyp tissues examined expressed mRNA of VPF/VEGF and KDR. In situ hybridization revealed that VPF/ VEGF mRNA-expressing cells were scattered in the edematous stroma of nasal polyps. In the adjacent sections, these cells showed the morphological features of plasma cells and expressed mRNA of immunoglobulin light chains. Human B cell leukemia and plasmacytoma cell lines expressed VPF/VEGF mRNA but human mast-cell leukemia and T cell leukemia cell lines did not. The alternatively spliced pattern of VPF/VEGF transcripts observed in nasal polyp tissues was consistent with that in plasmacytoma cell lines. Taken together, the VPF/VEGF mRNA-expressing cells in nasal polyps appeared to be plasma cells, suggesting that plasma cells may play an important role in the development of edema in chronic inflammation through the production of VPF/VEGF.
TL;DR: Results indicate that plasma cells from aggressive myeloma with high LDH express Fas antigen and undergo apoptosis through either Fas-mediated or Fas-independent pathways.
TL;DR: It is suggested that the ability of T cells to influence the differentiation state of transformed B cells may provide a mechanism by which malignant plasma cells found in the bone marrow could arise from clonotypically related less-mature B Cells found in both theBone marrow and periphery.
Abstract: Major interest in the analysis of mature plasma cell neoplasias of mice and humans has focused on identification of precursor cells that give rise to mature malignant plasma cells. Although several laboratories have recently suggested that such cells are present in the granulomas of pristane-treated mice and the bone marrow of some multiple myeloma patients, the in vivo cellular interactions required for their differentiation into mature plasma cell tumors remains unclear. Given the extensive interactions of peripheral T cells and normal B cells, we assessed the potential role of T cells in plasma-cell tumor development, by using a myc, raf-containing retrovirus, J3V1, to induce plasmacytomas in normal BALB/c mice, T-cell-deficient nude mice, and T-cell-reconstituted nude mice. The B-lineage tumors arising in normal BALB/c mice were uniformly mature plasmacytomas, most of which secreted immunoglobulin. In contrast, nude mice yielded predominantly non-immunoglobulin-secreting B-cell lymphomas with a phenotype characteristic of peripheral B cells. T-cell reconstitution of nude mice prior to tumor induction resulted in a shift from B-cell lymphomas to plasmacytomas. These results imply that transformation can occur prior to terminal differentiation of B cells and that such transformed cells can be driven to terminal differentiation by peripheral T cells. These findings further suggest that, in human multiple myeloma, the ability of T cells to influence the differentiation state of transformed B cells may provide a mechanism by which malignant plasma cells found in the bone marrow could arise from clonotypically related less-mature B cells found in both the bone marrow and periphery.
TL;DR: It is concluded that sIL‐6R can be used as a clinical factor correlated with the disease activity, at least in some patients with plasma cell neoplasias.
Abstract: We investigated the clinical significance of the serum soluble interleukin-6 receptor (sIL-6R) in 42 patients with plasma cell dyscrasias (27 with multiple myeloma (MM), 13 with monoclonal gammopathy of undetermined significance (MGUS), and two with plasma cell leukaemia (PCL)). Serum levels of sIL-6R in normal individuals were 77 +/- 21 ng/ml (mean +/- SD, n = 18); those in patients with MGUS and with MM were elevated (102 +/- 33 ng/ml, mean +/- SD, P < 0.05 and 126 +/- 60 ng/ml, mean +/- SD, P < 0.01, respectively). Significant correlations were not found between the serum levels of sIL-6R and known prognostic factors (C-reactive protein, haemoglobin levels, calcium, creatinine, beta 2-microglobulin, amounts of M-protein, or percentages of plasma cells in bone marrow). Elevated serum sIL-6R did not affect the survival of the patients with MM. Serial measurements of sIL-6R together with the clinical course of patients with plasma cell neoplasias revealed a good correlation between the sIL-6R level and disease activity. We conclude that sIL-6R can be used as a clinical factor correlated with the disease activity, at least in some patients with plasma cell neoplasias.
TL;DR: The tumor was removed surgically and did not recur during a 2-year follow-up with no radiation therapy, indicating this to be the ninth reported case of intracranial plasma cell granulation.
TL;DR: A 12-year-old, female spayed Chihuahua was diagnosed with nonsecretory multiple myeloma on the basis of multiple osteolytic lesions, histological evidence of plasma cell infiltrate on a bone biopsy, and absence of a monoclonal protein on serum and urine electrophoresis and was euthanized 2 weeks after presentation.
Abstract: A 12-year-old, female spayed Chihuahua was diagnosed with nonsecretory multiple myeloma on the basis of multiple osteolytic lesions, histological evidence of plasma cell infiltrate on a bone biopsy, and absence of a monoclonal protein on serum and urine electrophoresis. A 6-week course of prednisone therapy resulted in no clinical improvement and the dog was euthanized 2 weeks after presentation because of progressive neurological impairment. Bone marrow specimens were processed and stained for ultrastructural and immunohistologic evaluation. Staining with antisera to immunoglobulin (Ig) G, IgM, and IgA was negative. Tumor cells in both the pelvic and rib masses displayed prominent reactivity with an antibody specific for a canine beta 1 integrin similar to VLA-4; however, the tumor cells failed to stain with antibodies known to react predominantly with antigens on B-lymphocytes (major histocompatibility complex class II, CD45RA, and CD21) or T-lymphocytes (Thy-1). The tumor cells also failed to stain with an antibody specific for the beta-subunit (CD18) of the leukocyte integrins (D11/CD18). Ultrastructural studies performed on bone marrow specimens revealed a pleomorphic population of plasma cells with moderate amounts of rough endoplasmic reticulum, erythrophagocytosis, and lack of crystalline inclusions.
TL;DR: Phenotypic analysis of bone marrow and peripheral blood revealed that in multiple myeloma a great diversity exists in the phenotype of the cells considered to be involved, and the precursorMyeloma cell could not possibly be a pre-B cell or stem cell but has to be a mature B cell that has been in contact with antigen and has past through the phase of somatic mutation.
Abstract: Multiple myeloma is characterized by the monoclonal expansion of plasma cells in the bone marrow Although the predominant cell type is the plasma cell, the initial oncogenic transformation is considered to take place in a more immature B cell There is still much controversy about this precursor cell type Phenotypic analysis of bone marrow and peripheral blood revealed that in multiple myeloma a great diversity exists in the phenotype of the cells considered to be involved Because of the lack of a myeloma specific genetic lesion it is very difficult to trace back the cell in which the transforming event, leading to multiple myeloma, took place The only real clonal marker is the idiotype of the immunoglobulin molecule expressed by the myeloma cells With recombinant DNA technology it is now possible to produce clonal markers for each individual myeloma patient which recognize only the immunoglobulin genes expressed by the myeloma cell and its precursors The sequences of these myeloma immunoglobulin ge
TL;DR: A new, rapid and sensitive method is described to determine plasma cell isotype and clonality in bone marrow using flowcytometry using a new fixation and permeabilization reagent specific for plasma cells.
Abstract: In this paper we describe a new, rapid and sensitive method to determine plasma cell isotype and clonality in bone marrow using flowcytometry. With the use of a new fixation and permeabilization reagent (Permeafix), which preserves cell structure and morphology, and a monoclonal antibody (Mab) specific for plasma cells (B-B4), it has become possible to specifically select plasma cells and to determine the cytoplasmatic immunoglobulins by flowcytometry. Thirty successive bone marrow aspirates from multiple myeloma patients and patients with MGUS were studied as well as 10 bone marrow samples from patients with reactive plasmacytosis. Each sample was analysed both by immunofluorescence on cytospin smears and FACS analysis. There were no discrepancies between plasma cell isotype as determined by FACS and cytospin. Moreover, FACS analysis was shown to allow detection of very low numbers of plasma cells and to determine whether these plasma cells are mono- or polyclonal. Possible applications are discussed.
TL;DR: The infiltration of IgG2 and IgG4 bearing plasma cells into the skin of dogs with a range of cutaneous disorders was related to the selectively enhanced serum levels of these subclasses in the diseased dogs.
TL;DR: It is shown that blood B cells have IgH rearrangements identical to those expressed by the bone marrow plasma cells by using Ig Fingerprint and Allele-Specific Oligomer (ASO) polymerase chain reaction (PCR) methods.
Abstract: Previous reports have described the phenotypic and functional properties of monotypic late stage B cells in the blood of patients with multiple myeloma and have speculated that these B cells represent a malignant circulating component of myeloma. Here we show that blood B cells have IgH rearrangements identical to those expressed by the bone marrow plasma cells by using Ig Fingerprint and Allele-Specific Oligomer (ASO) polymerase chain reaction (PCR) methods. DNA from purified blood B ceils and bone marrow plasma cells taken at the same time, and blood B cells taken at subsequent patient visits was amplified using consensus IgH primers, or ASO primers. In 10/16 patients, a single IgH rearrangement was amplified from the bone marrow plasma cells. In all 10 of those patients the same clonotypic rearrangement was amplified from the purified blood B cells. The relationship of these clonal blood B cells to the malignant bone marrow plasma cells remains undetermined
TL;DR: B cell blasts generated by co-culturing B cells with an irradiated T cell clone activated with immobilized anti-CD3 differentiated into non-proliferating plasma cells as determined by poor thymidine incorporation, typical cellular morphology, intense expression of intracytoplasmic Igs, very high levels of surface CD38 and lack of surfaceCD20.
Abstract: B lymphocytes activated by T cells in secondary lymphoid organs mature into plasma cells after migration into the medullary cords of these organs, mucosal lamina propria or bone marrow. To analyze each step leading to plasma cell generation, we set up a two-step culture system of purified tonsillar B cells. In a primary stage, B cell blasts were generated by co-culturing B cells with an irradiated T cell clone activated with immobilized anti-CD3. In a secondary step, culturing these blasts on bone marrow stromal cells (BMSC) induced them to secrete large amounts of IgG, as well as some IgM and IgA. Other fibroblast-like cell lines were less efficient at sustaining the differentiation of blasts into Ig-secreting cells, suggesting that these are specific properties of BMSC. Addition of IL-3 and IL-10 further stimulated IgG secretion by B cell blasts cultured on BMSC, mostly the IgG1 subclass. These two cytokines probably acted through different pathways, as (i) the effect of IL-3 but not IL-10 was dependent upon prolonged T cell pre-activation and (ii) their combined stimulatory effect was additive. B cell blasts cultured on BMSC with a combination of IL-3 and IL-10 differentiated into non-proliferating plasma cells as determined by poor thymidine incorporation, typical cellular morphology, intense expression of intracytoplasmic Igs, very high levels of surface CD38 and lack of surface CD20.
Journal Article•
TL;DR: There are stable elevated levels of serum soluble IL-6 receptor (sIL-6R) in MM and MGUS, higher than levels seen in normals and a key element yet to be clearly defined is delineating the role of circulating plasma cells and their precursors in spreading the disease.
Abstract: Plasma cell atypia and cell proliferation changes which occur during the progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are accompanied by critical changes in neoplastic plasma cells and marrow stromal cells. Key elements include paracrine secretion of interleukin 6 (IL-6) by marrow stromal cells resulting from interleukin 1 beta (IL-1 beta) secreted by myeloma cells. In addition, there are stable elevated levels of serum soluble IL-6 receptor (sIL-6R) in MM and MGUS. They are higher than levels seen in normals. Oncogenes such as c-myc and ras probably play a major role as do cell adhesion molecules and loss of apoptosis. Immune regulatory cells may also play a role. A key element yet to be clearly defined is delineating the role of circulating plasma cells and their precursors in spreading the disease.
TL;DR: It is suggested that plasma cell dyscrasias should be classified simply into two main groups according to the need of immediate chemotherapy, and the appearance of new bone lesions and the increase of the M-component level remain the only two criteria that define malignant transformation.
Abstract: Plasma cell dyscrasias form a heterogeneous group of diseases characterized by the expansion of the number of monoclonal bone marrow plasma cells that produce monoclonal immunoglobulins. Sensitive electrophoretic methods have shown that the incidence of these diseases is as high as 5% in adult individuals. Thus, the majority of cases should be considered to be a normal phenomenon. A few transform into neoplastic diseases, plasma cells becoming responsible for lytic bone lesions, the hallmark of MM. The distinction of benign and malignant forms is frequently difficult at presentation. We can easily recognize solitary myeloma, overt myeloma and plasma cell leukaemia, which require immediate chemotherapy. Therapy could be safely withheld in all the remaining forms, which require only follow-up. Thus, we suggest that plasma cell dyscrasias should be classified simply into two main groups according to the need of immediate chemotherapy. The appearance of new bone lesions and the increase of the M-component level remain the only two criteria that define malignant transformation. Several clinical and laboratory prognostic parameters indicate the risk of transformation, and hence how close the follow-up of the patient should be. Parameters related to the expansion of the plasma cell clone (percentage of bone marrow plasma cells, M-component level, lytic bone lesions and beta 2-microglobulin) are not always very low and very high in the benign and malignant forms, respectively, and frequently overlap in patients with intermediate plasma cell expansions. On the contrary, all parameters related to the intrinsic malignancy of the plasma cells (plasma cell LI, Karyotypic abnormalities and molecular alterations) have, by definition, to be normal in the benign forms. MRI is a new tool that may, early on, reveal lytic bone lesions undetectable by conventional radiography.
TL;DR: The results highlight the idea that progressive periodontal disease is not only characterized by increased tissue inflammation, but, in addition, by significant changes in the proportion of specific inflammatory cells.
Abstract: Severe forms of periodontal disease are frequent in patients with acquired immunodeficiency syndrome (AIDS). Linear gingival erythema (LGE) is a progressive disease described in HIV-positive patients and is considered to be an early stage of necrotizing periodontitis. Although clinical and microbiological differences are reported in LGE and non-specific gingivitis (NSG), a comparative immunopathological approach of both has not been performed yet. The purpose of this study was to compare relative populations of T-lymphocytes, B-lymphocytes, neutrophils, macrophages and IgG bearing plasma cells in gingival biopsies from sites exhibiting LGE and from sites exhibiting NSG. A biotin-streptavidin amplified system was used for identification of the following antigens: CD3 (T-lymphocytes), CD20 (B-lymphocytes), elastase (neutrophils), CD68 (macrophages) and IgG (plasma cell's secretors of IgG). The results have demonstrated decrease proportions of T-lymphocytes, macrophages and high percentage of neutrophils and IgG bearing plasma cells in LGE. In contrast with NSG, many neutrophils cells in LGE were found inside oral gingival epithelium. Our results highlight the idea that progressive periodontal disease is not only characterized by increased tissue inflammation, but, in addition, by significant changes in the proportion of specific inflammatory cells. The high number of neutrophils along the gingival epithelium is probably associated with the severe gingival necrosis reported in AIDS patients.
TL;DR: A rare case of concurrent plasma cell granulomas (PCG) of the lung and the central nervous system (CNS) was reported in this article, where a 30-year-old man was presented with recurrent left headaches lasting for two years.
Abstract: A rare case of concurrent plasma cell granulomas (PCG) of the lung and the central nervous system (CNS) is reported. A 30-year-old man was presented with recurrent left headaches lasting for two years. Computerized tomographic (CT) scan and magnetic resonance imaging (MRI) of the head disclosed a process extending from the lateral aspect of the left cavernous sinus to the tentorium cerebelli and the infratemporal fossa through the foramen ovale. At the same time, chest-X ray and CT scan showed three symptomless masses of the pulmonary right lower lobe. Histological examination of cerebral samples and of one of the pulmonary nodules revealed the presence of a fibrous tissue containing numerous lymphocytes and plasma cells as well as remnants of vascular and respiratory structures. Immunohistochemical study proved these cells to be polyclonal. Ultrastructural analysis confirmed the presence of lymphoid cells and failed to disclose any argument for meningioma or histiocytosis X. The differential diagnostic problems of PCG are discussed as well as considerations about clinicopathological features, histogenesis and pathogenesis of inflammatory pseudotumours (IPT).
Journal Article•
TL;DR: A culture system in which naive B cells bearing a transgenic, chicken OVA-specific Ig differentiate to plasma cells in vitro after interaction with cOVA plus cOVA-specific helper T cells is established to study a primary immune response to an Ag, rather than to less physiologic polyclonal stimuli.
Abstract: We have established a culture system in which naive B cells bearing a transgenic, chicken OVA (cOVA)-specific Ig differentiate to plasma cells in vitro after interaction with cOVA plus cOVA-specific helper T cells. B cell-enriched populations from Ig-transgenic mice, but not from nontransgenic mice, proliferated after presenting nanomolar concentrations of cross-linked cOVA to DO11.10 (cOVA plus IAd-specific) T cells. After 6 to 9 days of culture with Ag and specific T cells, the B cells acquired a plasma cell phenotype and secreted the transgene-derived Ig at high levels. Engagement of B cell surface Ig was not essential for primary B cell differentiation. Differentiating B cells enlarged, clustered, and acquired two plasma cell markers, Syndecan and CD43. B cell CD45 isoform expression changed: the B220 isoform was lost in a T cell-dependent manner, whereas the CD45RB isoform was gained in a T-independent manner. Although unstimulated B cells survived less than 72 h in vitro, those in Ag-stimulated cultures showed reduced early death, a surge of proliferation at 3 to 5 days, and increased death late in the culture. Using a large population of naive B cells of defined antigenic specificity permits us to study a primary immune response to an Ag, rather than to less physiologic polyclonal stimuli. Because all steps of differentiation occurred in vitro, they are easily accessible for study. This coculture system provides an opportunity to observe Ag-specific T cell-B cell collaboration.
TL;DR: Most human tumours are monoclonal, which suggests that they originate from a single cell, and careful cytogenetic and molecular analysis has shown consistent reciprocal chromosomal translocations and partial and complete chromosomal deletions or duplications which reflect tumour clonality.
Abstract: Most human tumours are monoclonal, which suggests that they originate from a single cell. “Clonality” can be investigated by several techniques. In plasma a dominant monoclonal class of immunoglobulin suggests a neoplasm derived from a single altered plasma cell, which gives it a survival and growth advantage over non-neoplastic cells. In lymphoid malignancies, studies on rearrangements of genes coding for antigen receptors provide an excellent system of clonal markers, with consistent rearrangement of clonal immunoglobulin heavy chains (in B cell leukaemias and lymphomas)1 and T cell receptor s chains (in T cell tumours). In other tumours careful cytogenetic and molecular analysis has shown consistent reciprocal chromosomal translocations and partial and complete chromosomal deletions or duplications which reflect tumour clonality as well as indicating stretches of altered sequences of DNA that may have a role in the initial neoplastic change. Cytogenetic and DNA analysis has not yet, however, provided clonal markers for many solid tumours.2
An alternative approach, applicable only to females, is to take advantage of the phenomenon of “Lyonisation” (X inactivation mosaicism).3 4 Early in …
TL;DR: It is shown that it is the low density of surface antigen expression that explains the discrepancy in B cell numbers identified by surface immunoglobulin expression versus B cell markers, and that only the highly sensitive flow cytometric analysis can detect such low-density expression.