Showing papers on "Plasma cell published in 1994"
TL;DR: Stable or transient transfection of Blimp-1 into B cell lymphoma lines leads to the expression of many of the phenotypic changes associated with B cell differentiation into an early plasma cell stage, including induction of J chain message and immunoglobulin secretion, up-regulation of Syndecan-1, and increased cell size and granularity.
782 citations
TL;DR: In this article, the extent of bone marrow angiogenesis, evaluated as microvessel area, and the proliferating (S-phase) fraction of marrow plasma cells was evaluated as labelling index (LI), in patients with multiple myeloma (MM) and in those with monoclonal gammopathies of undetermined significance (MGUS).
Abstract: Summary
Tumour growth is angiogenesis-dependent. We found a high correlation between the extent of bone marrow angiogenesis, evaluated as microvessel area, and the proliferating (S-phase) fraction of marrow plasma cells, evaluated as labelling index (LI), in patients with multiple myeloma (MM) and in those with monoclonal gammopathies of undetermined significance (MGUS). Angiogenesis itself was significantly associated with active as opposed to non-active MM and MGUS. The highest microvessel area accompanied rapidly progressive MM with the highest LI. When a cut-off value of 2% or greater of the microvessel area was used, most patients with active MM were classified correctly. The risk of active disease in patients with MM increased in parallel with the microvessel area. A causal relationship between plasma cell growth, activity phase in MM and marrow angiogenesis is suggested. Since angiogenesis proceeds in step with the enlargement of plasma cell tumours and the activity phase in MM, its measurement could be a useful prognostic marker in patients with plasma cell proliferative disorders.
603 citations
TL;DR: The authors' studies indicate that the HM1.24-related protein represents a specific marker of late-stage B-cell maturation and potentially serves as a target antigen for the immunotherapy of multiple myeloma and related plasma cell dyscrasias.
234 citations
TL;DR: The results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo, and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.
161 citations
TL;DR: Results suggest that BSAP activity is a rate-limiting regulator of B cell proliferation and treatment with the antisense BSAP oligonucleotide downregulated Ig class switching induced by interleukin 4 plus LPS.
Abstract: The B cell-specific activator protein (BSAP) is a DNA-binding transcription factor expressed in pro-B, pre-B, and mature B cells, but not in plasma cells. In this study, we explored the role of BSAP in B cell function by assessing how the content of this protein varies in cells driven by proliferative stimuli and, conversely, how artificial manipulation of BSAP activity affects cell proliferation. We found that BSAP activity of nuclear extracts increased when B cells were activated by mitogen (lipopolysaccharide [LPS]), antigen receptor-mediated signaling (surface immunoglobulin D [IgD] cross-linking) or T cell-dependent stimulation (CD40 cross-linking). We could suppress BSAP activity by exposure of B cells to phosphorothioate oligonucleotides antisense to the BSAP translation initiation start site, whereas control oligonucleotides were virtually inactive. Antisense-induced BSAP suppression was associated with a striking reduction in LPS-induced proliferation of splenic B cells and in the spontaneous proliferation of B lymphoma cells (CH12.LX), but the antisense oligonucleotide had virtually no effect on proliferation of two cell lines lacking BSAP: the T lymphoma line EL-4 and the plasma cell line MOPC-315. Overexpression of BSAP in splenic B cells or de novo expression in MOPC-315 plasma cells induced by transfection of a BSAP expression plasmid stimulated cell proliferation. Taken together, these results suggest that BSAP activity is a rate-limiting regulator of B cell proliferation. We also found that treatment with the antisense BSAP oligonucleotide downregulated Ig class switching induced by interleukin 4 plus LPS. This effect may be secondary to reduced proliferation or could be mediated through BSAP binding sites in the IgH locus.
137 citations
Journal Article•
TL;DR: The findings show that Rb1 and p53 inactivation are associated with aggressive plasma cell dyscrasias, suggesting a role for these lesions in tumor progression rather than initiation.
Abstract: The role of loss or inactivation of the retinoblastoma (Rb1) and p53 tumor suppressor genes in the pathogenesis of various human malignancies has been well established, yet little is known regarding plasma cell dyscrasias. In the present study, the loss of Rb1 protein expression, and the presence of Rb1 gene rearrangements as well as the presence of p53 somatic mutations (exons 5 through 9) were investigated in a panel of plasma cell dyscrasias, including 15 monoclonal gammopathies of undetermined significance (MGUS), 63 multiple myelomas (MM), and 18 plasma cell leukemias (PCL). In the same panel of cases, we established the frequency of ras oncogene mutations, the main genetic lesion associated with MM. We report that loss of Rb1 protein and p53 mutations are detectable in 34.7 and 9.8% of MM and PCL primary cases; no lesion was found in MGUS. In advanced stage MM, and PCL cases, Rb1 and p53 inactivation, as well as ras mutations were detected. Our findings show that Rb1 and p53 inactivation are associated with aggressive plasma cell dyscrasias, suggesting a role for these lesions in tumor progression rather than initiation.
109 citations
TL;DR: An antiserum is developed which recognizes the human Btk protein and it is shown that normal human tonsillar B cells, peripheral blood monocytes and myeloid cells express the protein, whereas tonsil‐derived T cells do not.
Abstract: Defects in the gene encoding Bruton's tyrosine kinase (Btk), normally expressed in B cells, cause X-linked agammaglobulinemia (XLA). The phenotype of XLA is characterized by a lack of circulating B cells and immunoglobulin. It has been suggested that B cell maturation from the pre-B cell stage to more mature stages is dependent on the appropriate expression of this gene. The Btk mRNA is expressed in B cells and myeloid cells, but protein expression in relation to B cell maturation has not been determined. Moreover, expression of the Btk protein has so far only been investigated in human Epstein-Barr virus-transformed B cell lines, and in murine splenocytes and B cell lines. We have developed an antiserum which recognizes the human Btk protein and shown that normal human tonsillar B cells, peripheral blood monocytes and myeloid cells express the protein, whereas tonsil-derived T cells do not. We also show that the protein is present in early and mature human B cell lines, but is absent in terminally differentiated plasma cell lines. Furthermore, expression is reduced or absent in three B lineage cell lines derived from two patients with defined genetic mutations in Btk and suffering from XLA.
103 citations
01 Mar 1994
TL;DR: The reduction in J chain mRNA expression in duodenal IgA plasma cells in IgAN argues against the gastrointestinal lamina propria as the source of glomerular pIgA.
Abstract: Expression of J chain mRNA in duodenal IgA plasma cells in IgA nephropathy. Glomerular IgA in IgA nephropathy (IgAN) is at least in part polymeric, and is thought to derive from the mucosal IgA system in view of the association between mucosal infection and haematuria in this condition. To investigate this hypothesis, an in situ hybridization (ISH) technique was developed for the detection of J chain mRNA, the expression of which has been correlated with the secretion of high level polymeric immunoglobulin (pIg). Endoscopic duodenal biopsies from ten patients and matched controls were examined by: (i) two color immunofluorescence (IF); (ii) ISH; and (iii) combined ISH and IF, to permit simultaneous identification of plasma cell type. IF revealed a reduction in the percentage of IgA plasma cells (P
85 citations
TL;DR: The ontogeny of B cells and plasma cells in carp (2 weeks-16 months) was studied and increased during the development of the carp reaching a plateau at about 3 months of age for plasma cells and around 8 months ofAge for B cells.
75 citations
TL;DR: The assessment of the total proliferative rate of bone marrow samples does not reflect either the proliferation of normal cells or that of neoplastic plasma cells but will depend on the proliferation rate and the percentage of each population within the sample, which can be assessed by the CD38/propidium iodide double staining technique.
Abstract: In the present paper a CD38/propidium iodide double staining technique is described which separately assesses the cell cycle distribution of myelomatous plasma cells from that of the residual normal hemopoietic cells. For this purpose, bone marrow (BM) cells from a group of 42 untreated multiple myeloma patients were analyzed. Of these, 23 cases were aneuploid (55%) and 19 diploid (45%). The use of the CD38/propidium iodide double staining method allowed a clear separation between CD38 strong positive cells from the remaining bone marrow populations, cell sorting experiments confirming that plasma cells were almost exclusively contained in the former fraction where they represented 97 +/- 2% of the total cells sorted. In all cases, the S-phase in plasma cells and in the remaining normal hemopoietic bone marrow cells was assessed, being higher in normal hemopoietic cells (8.0 +/- 6.3%) than in plasma cells (3.3 +/- 2.6%, P 0.10); this work therefore shows that the assessment of the total proliferative rate of bone marrow samples does not reflect either the proliferation of normal cells or that of neoplastic plasma cells but will depend on the proliferative rate and the percentage of each population within the sample, which can be assessed by the technique described here.
75 citations
TL;DR: Results indicate that other mechanisms of resistance must be involved in MM apart from MDR, and the role of MDR status at this stage of disease may be biased by the major contribution of dexamethasone to induction of response by VAD in MM patients.
Abstract: PURPOSETo assess whether the presence of enhanced multiple drug resistance (MDR)-1 gene expression in multiple myeloma (MM) patients predicts survival, as well as response to vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy.PATIENTS AND METHODSSixty-three MM patients refractory to alkylating therapy were studied. The presence of the MDR-1 gene product, a 170-kd glycoprotein (P-170), was analyzed in bone marrow plasma cells by means of the alkaline phosphatase (APAAP) technique using the P-170-specific monoclonal antibody (MoAb) C219. The prognostic value of MDR-1 gene expression, examined before VAD treatment, was compared with other established prognostic factors including beta 2-microglobulin, albumin, lactate dehydrogenase (LDH), and the plasma cell labeling index.RESULTSFifty-nine percent of all samples were P-170-positive. No association could be demonstrated between response to VAD and MDR-1 gene expression (chi 2 P = .359), in contrast to high serum beta 2-microglobulin levels, which ...
TL;DR: The identification of PC-1 as an NTPPPH expressed in cells derived from bone and cartilage may prove useful in furthering the understanding of the role of NTP PPH in physiologic and pathologic mineralization.
Abstract: A bone and cartilage enzyme with both 5'-nucleotide phosphodiesterase I and nucleotide pyrophosphohydrolase (NTPPPH) activity modulates physiologic mineralization and pathologic chondrocalcinosis by generating inorganic pyrophosphate. We hypothesized that, as for alkaline phosphatase, expression of an NTPPPH gene can be shared by cells from bone, cartilage, and liver and by certain leukocytes. Recently, we demonstrated the hepatocyte and murine plasma cell membrane glycoprotein PC-1 to have both 5'-nucleotide phosphodiesterase I and NTPPPH activity. We detected polypeptides cross-reactive with PC-1 in human U20S osteosarcoma cells, articular chondrocytes, homogenized human knee cartilages, human knee synovial fluids, hepatoma cells, and murine plasmacytoma cells. Constitutive low abundance PC-1 mRNA expression was detected in U20S cells and chondrocytes by a nested RNA-PCR assay and by Northern blotting. TGF beta is known to substantially increase NTPPPH activity in primary osteoblast cultures. We demonstrated that TGF beta 1 increased NTPPPH activity and the level of PC-1 mRNA and immunoprecipitable [35S]-methionine-labeled PC-1 polypeptides in U20S cells. The identification of PC-1 as an NTPPPH expressed in cells derived from bone and cartilage may prove useful in furthering the understanding of the role of NTPPPH i n physiologic and pathologic mineralization.
TL;DR: The patterns of dendritic network seen in the hyaline vascular type, together with the absence of sinus lining cells, appear to favour the hamartoma theory proposed for this variant of Castleman's disease.
Abstract: Twenty-seven cases of the hyaline vascular variant and 10 cases of the plasma cell variant of Castleman's disease were studied with the paraffin resistant monoclonal antibodies Ki-FDC1p and/or Ki-M4p against follicular dendritic cells. Studies with the monoclonal antibody Ki-M9, for the detection of sinus lining cells, were also performed on the available frozen tissue in four cases of the hyaline vascular variant. In nine of the 10 plasma cell variant cases, the predominant type of follicular dendritic cell network was similar to that seen in normal or reactive germinal centres. In contrast, the hyaline vascular variant demonstrated either an expanded, disrupted, follicular dendritic cell network (10 cases) or multiple tight collections of follicular dendritic cells (16 cases). Sinus lining cells were not detected in the four cases studied. The difference in the predominant type of dendritic meshwork is an additional distinguishing feature to separate the plasma cell and hyaline vascular variants of Castleman's disease. The patterns of dendritic network seen in the hyaline vascular type, together with the absence of sinus lining cells, appear to favour the hamartoma theory proposed for this variant.
Journal Article•
TL;DR: Findings indicate that, although IgM-positive clonogenic cells may exist, it is unlikely that they are involved in continuous maintenance of the malignant isotype-switched cell population.
Abstract: The identifiable neoplastic cell in multiple myeloma is the plasma cell, which usually synthesizes and secretes a monoclonal immunoglobulin. However, there exists the possibility that the neoplastic event has occurred in a less mature clonally-related cell, such as a B lymphocyte, prior to Ig class switching. Since the presence of such a clonogenic cell could influence design of therapy, particularly with monoclonal antibodies, we have used the analysis of tumour-related VH genes to approach this question. Cloning and sequencing of PCR products from VH genes of tumour cells obtained from 4/4 patients with myeloma revealed significant mutation of the genes as compared to germ line sequences. In all cases the mutations were scattered throughout the variable region, with a pattern which did not indicate a role for antigen in selection. Importantly for therapy, multiple VH sequences from all patients were completely homogeneous, with no intraclonal variation. These findings indicate that, although IgM-positive clonogenic cells may exist, it is unlikely that they are involved in continuous maintenance of the malignant isotype-switched cell population. One possibility is that the B-cell progenitor population has to undergo further chromosomal changes to generate the malignant cell, and that this occurs at a more mature stage; in this case, antibody therapy should be aimed primarily at the more differentiated cells.
TL;DR: The results indicate that GH and IGF-I may play important roles in plasma cell responses and enhance production and proliferation in human plasma cell lines generated in vitro.
TL;DR: As middle-dosage corticosteroid therapy is not cytotoxic, it is useful for the treatment of pulmonary plasma cell granuloma, especially in multifocal, unresectable, and/or relapsing cases.
TL;DR: The results suggest that plasma cell malignancy is another AIDS-associated neoplasm, occurrence in this group of patients is not only coincidental.
Abstract: This report describes the occurrence of plasma cell neoplasia in three young HIV-positive males. Two patients presented with massive ascites. On cytologic examination of the fluid, many immature plasma cells were noted. Genotyping of fluid demonstrated clonal rearrangement of immunoglobulin heavy and kappa light chain genes in both cases. Postmortem examination on one of these revealed neoplastic plasmacellular infiltrate in various organs, including the bone marrow. The third case presented with a hemorrhagic, rapidly enlarging gingival mass with a histologic appearance of an undifferentiated neoplasm. Immunoperoxidase studies revealed positive staining only for epithelial membrane antigen. On flow cytometry, the neoplastic cells did not mark with leukocyte common antigen or any of the B- or T-cell markers. Cytoplasmic kappa light chain restriction, as well as genotypic studies, confirmed the diagnosis of anaplastic plasmacytoma. In two cases a clonal population was detected using a probe to the terminal repeat region of the Epstein-Barr virus. These results suggest that plasma cell malignancy is another AIDS-associated neoplasm. Its occurrence in this group of patients is not only coincidental.
TL;DR: The case of a patient who developed a posttransplantation lymphoproliferative disorder that was composed of multiple plasmacytomas located in the abdomen and urinary bladder after liver transplantation is presented.
Abstract: Background. Lymphoproliferative disorders that occur in patients receiving cyclosporine for immunosuppression after solid organ transplantation typically are B-cell neoplasms associated with Epstein-Barr virus (EBV), which may be polyclonal or monoclonal in origin. Although these tumors may have partial B-cell differentiation, (manifested as plasmacytoid features), terminal differentiation to plasma cells that secrete a monoclonal immunoglobulin is rare. The case of a patient who developed a posttransplantation lymphoproliferative disorder that was composed of multiple plasmacytomas located in the abdomen and urinary bladder after liver transplantation is presented. The patient also had high levels of an immunoglobulin-Gk monoclonal paraprotein.
Methods. The plasmacytoma was examined for the presence of EBV by both polymerase chain reaction and in situ hybridization, and the possibility of a codon-12 mutation in the ras gene was investigated by digestion of DNA amplification products with the HpaII-restriction endonuclease.
Results. Epstein-Barr virus genomes were demonstrated by DNA amplification of sequences in the long, internal, direct repeat region, and in situ hybridization showed expression of EBV RNA transcripts that annealed to an EBER-1 probe. Immunohistochemistry showed clonally restricted expression of K light chains but failed to reveal evidence of expression of the latent membrane protein 1 encoded by EBV. Mutations of codon-12 in the H-ras gene were not detected.
Conclusions. Resolution of the tumor and the paraprotein after radiation and reduction of immunosuppression indicates that terminal plasmacytic differentiation does not necessarily portend an unfavorable prognosis, even in a clonal lesion.
TL;DR: Evidence is provided for autocrine and possibly an additional paracrine regulatory loop in plasma cell neoplasias and CMD and in several patients with CMD, peripheral blood cells were shown to produce extremely high levels of IL-6.
Abstract: Functioning as a B-cell growth and differentiation factor, interleukin-6 (IL-6) may play an important role in the pathophysiology of B-cell tumors. The capacity for IL-6 secretion was evaluated in 58 patients with various B-cell leukemias/lymphomas and in four patients with Castleman's disease (CMD). Cell populations from various sites including peripheral blood, bone marrow, lymph nodes, and osteolytic bone lesions were cultured and tested for spontaneous or IL-1Β/ TNFα-induced IL-6 production in a sensitive bioassay. No significant IL-6 levels were released by the tumor cells in any of the B-cell leukemias or lymphomas tested, including hairy cell leukemia (HCL) and B-cell chronic lymphocytic leukemia (B-CLL). In contrast, purified malignant plasma cells were found to secrete IL-6, strengthening the idea that an autocrine pathway for growth regulation in multiple myeloma (MM) exists. For the first time, in several patients with CMD, peripheral blood cells were shown to produce extremely high levels of IL-6, the pathogenetic significance of which remains to be elucidated. However, similar observations were very occasionally made in MM patients. Therapy with corticosteroids strongly inhibited this IL-6 production. These data provide evidence for autocrine and possibly an additional paracrine regulatory loop in plasma cell neoplasias and CMD.
TL;DR: A patient is reported who had two plasma cell granulomas in the spinal meninges and one in the anterior cerebral falx, and the histological findings that differentiate this rare lesion from other central nervous system lesions are discussed.
Abstract: Plasma cell granulomas of the central nervous system are exceedingly rare. Of the six well-documented cases that have been published to date, five plasma cell granulomas were intracranial and one was located in the spinal meninges. Multiple plasma cell granulomas of the central nervous system have not previously been reported. We now report a patient who had two plasma cell granulomas in the spinal meninges and one in the anterior cerebral falx. The histological findings that differentiate this rare lesion from other central nervous system lesions, such as plasmacytoma and meningioma, are discussed with a review of the literature.
TL;DR: It is concluded that T. canis‐induced pulmonary inflammation affects the permeability of the microvasculature and is expressed by interstitial oedema and plasma exudation in the airway lumen, both phenomena occur also in allergic asthma.
Abstract: The pulmonary immuno-inflammatory reaction and its effect on microvascular integrity was studied in Toxocara canis infected BALB/c mice. The investigation aimed to compare changes in lung histology and composition of bronchoalveolar lavage fluid (BALF) caused by T. canis infection with those described to occur in allergic asthma. Groups of (non)-infected mice (1000 ova) were investigated until 90 days post infection (p.i.). Migration of the larvae through the lungs was followed by a rapidly progressing multifocal interstitial and alveolar inflammation. Eosinophils and lymphocytes formed perivascular and partially peribronchial mixed cellular infiltrates. Lymphocytes with plasma cell morphology staining intracellularly for either alpha, epsilon or gamma immunoglobulins were demonstrated. BALF, collected from mice infected with either 250, 500 or 1000 ova was analysed at 14 and 28 days p.i. A dose-related increase in cell numbers and in albumin and IgA concentration was observed. IgE increase was independent of the infective dose. Peak values were measured at 14 days p.i. Albumin increase in lung homogenate was highest at 28 days p.i. 30% of the lymphocytes consisted of T cells carrying Thy-1,2 and L3T4 surface antigens. It is concluded that T. canis-induced pulmonary inflammation affects the permeability of the microvasculature. This is expressed by interstitial oedema and plasma exudation in the airway lumen. Both phenomena occur also in allergic asthma. It is suggested that increased permeability of the microvasculature is mediated by T cells and eosinophils.
TL;DR: Data indicate that the IL‐2Rα and IL-2Rβ in mature lymphoid neoplasms was expressed independently each other and was associated with the particular phenotypical characteristics of neoplastic cells, respectively.
Abstract: We investigated the expression of interleukin-2 receptors (IL-2R) in 60 adult patients with mature lymphoid neoplasms by flow cytometric analysis, using two monoclonal antibodies, anti-Tac for IL-2R alpha-chain (IL-2R alpha) and Mik-beta 1 for IL-2R beta-chain (IL-2R beta). Among B-cell malignancies, IL-2R alpha was found in 13/25 (52%) cases of chronic lymphocytic leukemia (CLL) and its variants, 3/14 (21%) of a heterogeneous group of non-Hodgkin's lymphoma (NHL) and none of the plasma cell diseases. IL-2R beta was not observed in any of B-cell neoplasms. IL-2R alpha was more frequently expressed in CD11b(+) B-cell neoplasms than in CD11b(-) (P < 0.05). In T-cell disorders, all three cases of adult T-cell leukemia/lymphoma expressed IL-2R alpha but not IL-2R beta. IL-2R beta was detected in 3/8 cases of CLL and 2/3 of NHL and none of these cases expressed IL-2R alpha. CD8(+) malignant T-cells commonly displayed IL-2R beta. These data indicate that the IL-2R alpha and IL-2R beta in mature lymphoid neoplasms was expressed independently each other and was associated with the particular phenotypical characteristics of neoplastic cells, respectively.
TL;DR: The radiographic and histopathological findings indicated the development of bone destruction at 10 days which continued until 60 days; tissue repair began to take place after 90 days; the results suggested that macrophages had a close relation to bone destruction and that plasma cells might participate in tissue repair rather than theDevelopment of periapical lesions.
Abstract: – To investigate the role of plasma cells and macro-phages in the development of periapical lesions, we immunohistochemically examined the distribution of these inflammatory cells in experimental induced rat periapical lesions after pulpectomy. The number of EDI-positive mononuclear cells increased rapidly, reached a plateau which remained stable between days 10 and 60, and subsequently decreased. Immunoglobulin (Ig)-bearing plasma cells appeared alter 60 days, and, of these, IgG-bearing plasma cells were predominant after 90 days. The radio-graphic and histopathological findings indicated the develop-ment of bone destruction at 10 days which continued until 60 days; tissue repair began to take place after 90 days. The results suggested that macrophages had a close relation to bone destruc-tion and that plasma cells might participate in tissue repair rather than the development of periapical lesions.
TL;DR: The authors extensively review the role of cytokines in lymphomas because this may lead to major advances in the understanding of the molecular processes involved in the histopathogenesis of lymphomas.
TL;DR: It is suggested that ras mutations represent a late molecular lesion and may be implicated in tumor progression rather than tumor initiation, and adverse prognostic parameters are suggested.
Abstract: N- and K-ras oncogene mutations represent the most frequent molecular lesions in plasma cell dyscrasias. They are not randomly distributed since they are detectable in multiple myeloma (MM) (9-31%) and plasma cell leukemia (PCL) (30%), and not in monoclonal gammopathy of undetermined significance (MGUS) and solitary plasmacytoma (SP). Codons 12, 13 and 61 of N- and K-ras genes have been found mutated. Mutations affecting codon 61 of N-ras gene are the most frequent finding. A heterogeneous pattern of mutations is described with a prevalence of purine-pyrimidine trans versions. Ras gene mutations have been predominantly detected in myelomas characterized by an advanced stage disease, and adverse prognostic parameters. These findings suggest that ras mutations represent a late molecular lesion and may be implicated in tumor progression rather than tumor initiation.
Journal Article•
TL;DR: KHM-11 is a CD45-positive immature plasma cell line and should be a useful tool for understanding not only the pathogenesis of aggressive multiple myeloma with high LDH but also for understanding the mechanism which underlies the terminal differentiation of B-cells.
Abstract: A myeloma cell line (KHM-11) was established from the pleural effusion of a patient with IgA-kappa type aggressive myeloma with high serum lactate dehydrogenase who was extremely resistant to vincristin, adriamycin and dexamethasone combination therapy (VAD). The morphology of fresh tumor cells and KHM-11 was plasmablast according to Greipp's criteria. In addition to the expression of regular plasma cell antigens, CD38 and PCA-1, CD45 was found on both fresh cells and KHM-11. Other T- or B-cells antigens, such as CD2, 4, 8, 19, and 20 were negative. Cytoplasmic immunoglobulin kappa light chain in KHM-11 was found by flowcytometry. Southern blot analysis revealed that fresh sample and KHM-11 shared the same immunoglobulin gene rearrangement. IL-6 was found in the culture supernatant of KHM-11, and this supernatant stimulated the growth of this cell line, indicating an IL-6 autocrine mechanism. These findings indicate that KHM-11 is a CD45-positive immature plasma cell line. As far as we know, there is no report of CD45-positive myeloma cell line. KHM-11 should be a useful tool for understanding not only the pathogenesis of aggressive multiple myeloma with high LDH but also for understanding the mechanism which underlies the terminal differentiation of B-cells.
Journal Article•
TL;DR: This study shows that the amyloidogenic cell clone is constituted by at least the following cell populations: a fraction of bone marrow cells (lymphoid, lymphoplasmacytoid cells and PC) and a subset of peripheral blood post-switched B lymphocytes.
TL;DR: GM1 enhanced immunoglobulin (Ig) production and proliferation in the human plasma cell lines, IM‐9 and AF‐10, while other gangliosides tested, indicating that GM1 may be an important regulator of plasma cell responses.
Abstract: The effects of gangliosides on human plasma cell responses were studied. Among the various gangliosides tested, only GM1 enhanced immunoglobulin (Ig) production and proliferation in the human plasma cell lines, IM-9 and AF-10, while other gangliosides (GM2, GM3, GD1a, GD1b, GD3, GT1b, and GQ1b) had no effect. Among the various cytokines tested, including interleukin (IL)-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, interferon (IFN)-α and IFN-γ, only IL-6 enhanced Ig production and proliferation in IM-9 and AF-10 cells. However, the enhancement of plasma cell responses by GM1 was specific and was not mediated by IL-6, since GM1 activity was blocked by anti-GM1 monoclonal antibody (mAb), but not by control IgM, anti-IL-6 Ab or the anti-IL-6 receptor mAb, PM1. Conversely, the enhancement by IL-6 was blocked by anti-IL-6 Ab and PM1, but not by anti-GM1 mAb. GM1, but not other gangliosides, also enhanced Ig production and proliferation in freshly separated plasma cells from patients with plasma cell leukemia and in plasma cells generated in vitro. These actions of GM1 were specifically blocked by anti-GM1 mAb, but not by anti-IL-6 Ab or PM1. These results indicate that GM1 may be an important regulator of plasma cell responses.
TL;DR: Plasma cell granuloma is a rare benign lesion found most frequently in the lungs, and a few cases have been described in the head and neck, and in the middle ear and mastoid, a case of plasma cellgranuloma was reported by Benton et al.
Abstract: Background. Plasma cell granuloma is a rare benign lesion which is found most frequently in the lungs, and a few cases have been described in the head and neck. In the middle ear and mastoid, a case of plasma cell granuloma was reported by Benton et al.
Methods and Results. A 24-year-old woman was seen with a 7-month history of otalgia and decreased hearing. A computed tomographic (CT) scan showed a soft tissue mass occupying most of the mastoid bone. The mass and the contiguous dura were enhanced homogeneously on magnetic resonance imaging (MRI) scan. Microscopic examination showed plasma cell aggregates mixed with other inflammatory cells and Russell's bodies in a fibrous stroma. Immunoperoxidase studies revealed intracytoplasmic kappa and lambda light chains, and the lesion was confirmed as nonneoplastic and of polyclonal origin (ie, plasma cell granuloma). The patient was treated with conservative surgical excision (a canal-down mastoidectomy) and postoperative radiotherapy (5,040 cGy in 28 fractions) and remains free of disease 1 year after treatment.
Conclusions. A case of plasma cell granuloma is reported, and we believe this is the second case report of plasma cell granuloma affecting the temporal bone. © 1994 John Wiley & Sons, Inc.
TL;DR: IgG and IgE may be involved in a specific way in this condition; formation of immune complexes with leishmanian antigens leads to immunologically mediated lysis of the host macrophages.
Abstract: Tissues from 10 patients with localized leishmania lymphadenitis were stained by immunoperoxidase technique for leishmanian antigens, immunoglobulins (Ig), complement, components, alpha 1-antitrypsin, and fibrin and by routine and chloroacetate esterase techniques. Lymph nodes with leishmania lymphadenitis showed a granulomatous process with a varying degree of necrosis, leishmanian amastigotes, abundant plasma cells, and focal fibrosis. Leishmanian antigens stained by rabbit anti-Leishmania tropica antiserum was detected in lymph nodes with granulomatous lymphadenitis (eight cases examined) and in a skin lesion but not in a lymph node showing only nonspecific hyperplasia. Positive antigen staining was seen in leishmanian amastigotes, granulomata, and (in three cases) vascular smooth muscles. Dominant plasma cell classes were IgG and IgE. Macrophages and granulomata stained positively for IgG and IgE (but not for IgM or IgA), faintly for C3, and strongly for alpha 1-antitrypsin. Mast cells were few. IgG and IgE may be involved in a specific way in this condition; formation of immune complexes with leishmanian antigens leads to immunologically mediated lysis of the host macrophages. This finding is important for the understanding of the pathogenesis of leishmania lymphadenitis and for effective elimination of the parasites.