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At least 199 records · Page 11Linked to original sources
PubMed2002

Leukemic B cells clonally identical to myeloma plasma cells are myelomagenic in NOD/SCID mice.

OBJECTIVE: In multiple myeloma (MM), the immunoglobulin gene rearrangement characterizing malignant plasma cells is unique. For a patient with multiple myeloma who underwent a B-cell leukemic blast transformation, using the immunoglobulin molecular signature, we characterized the clonal relationship to autologous plasma cells and the impact on normal polyclonal B-lymphocyte populations. METHODS: Single-cell reverse transcriptase polymerase chain reaction (RT-PCR)/PCR was used to determine the clonal relationship between autologous MM plasma cells and leukemic B cells. A murine xenograft model was used to determine the myelomagenic potential of the leukemic B cells. RESULTS: Single-cell analysis showed that circulating leukemic-phase cells were clonotypic, with an IgH VDJ sequence identical to that of diagnosis plasma cells. Analysis of IgH transcripts indicates MM clonal dominance over normal B-cell components of the immune system at diagnosis and during leukemic disease. Leukemic B cells were xenografted to irradiated NOD/SCID mice, leading to lytic bone lesions and clonotypic cells in murine BM. Although human cells in murine BM expressed CD138, a marker largely absent from ex vivo leukemic cells, the expression of CD45, CD19, and CD20 confirmed that engrafting cells were mature, probably late-stage B cells rather than plasma cells. CONCLUSIONS: Leukemic B cells are able to exert strong clonal dominance over normal components of the immune system, colonize the murine BM in a xenograft model, and disrupt normal bone metabolism leading to lytic bone lesions. This supports the hypothesis that clonotypic MM B cells are reservoirs of disease that persist throughout therapy and give rise to relapse.

Animals↗
PubMed2001

Successful therapy of pure red cell aplasia secondary to plasma cell dyscrasia with bolus methylprednisolone.

A 65-year-old man, who is a Jehovah's Witness, was admitted to our hospital due to progressive anemia following a four-year history of biclonal gammopathy of no clinical significance. He was diagnosed with pure red cell aplasia (PRCA) associated with plasma cell dyscrasia. Despite a markedly decreased red blood cell count (hematocrit 5.6%), the patient refused transfusion. He was intravenously administered bolus methylprednisolone. Reticulocytosis and recovery from anemia were observed on day 7 after the start of therapy. Secondary PRCA following plasma cell dyscrasia is a rare disorder; the treatments for this rare condition are discussed.

Aged↗
PubMed1993

Detection of human papillomavirus type 16 in plasma cells.

Chronic benign plasma cell tumor of the cervix, also called chronic plasma cell cervicitis, is a rare disease of unknown etiology, characterized by a heavy infiltration of plasma cells forming granulation tissue. To identify infectious agents associated with this disease, we extracted and analyzed DNA from the 17-year-old paraffin section of the original case report and from granulation tissue surgically removed from a patient at our institution with a chronic benign plasma cell tumor. The DNA from both patients was shown by a polymerase chain reaction (PCR) technique to contain a human papillomavirus 16 (HPV 16) sequence. Genomic Southern analysis of the fresh-frozen tissue confirmed the initial PCR finding. In situ hybridization further demonstrated that the HPV 16 was present in the plasma cells and not a contaminant from the surrounding epithelial tissue. The etiological role of HPV 16, an oncogenic virus associated with cervical carcinoma, in this disease is not yet clear. Our results, however, suggest that the types of cells that are infected by HPV may include cells of lymphoid origin, and that HPV may be associated with chronic benign plasma cell tumors of the cervix.

Aged↗
PubMed1999

Monoclonality of infiltrating plasma cells in primary pulmonary nodular amyloidosis: detection with polymerase chain reaction.

AIMS: To investigate the relation between localised amyloidosis and immunocytic dyscrasia. METHODS: Open lung biopsy specimens from a 72 year old man with multiple nodules in the right middle and lower lung were stained with haematoxylin-eosin, Congo red, and antibodies against IgG, IgA, IgM, and kappa and lambda light chains. Semi-nested PCR amplification for the immunoglobulin heavy chain (IgH) gene was performed using consensus primers for the VDJ region of the IgH gene, FR3A, LJH, and VLJH. RESULTS: The biopsy specimens contained eosinophilic amorphous material stained with Congro red and anti-kappa light chain, and surrounded by inflammatory cells intermingled with plasma cells. Plasma cells in the adjacent amorphous material showed cytoplasmic staining with anti-kappa. Polymerase chain reaction revealed a discrete amplified band of apparently uniform size with background smear. CONCLUSIONS: Primary AL type localised amyloidosis involves local accumulation of monoclonal plasma cells and their secreted products, as in nodular cutaneous amyloidosis. Localised AL type nodular amyloidosis is a separate entity in amyloidosis.

Aged↗
PubMed2004

Neural cell adhesion molecule expression in plasma cells in bone marrow biopsies and aspirates allows discrimination between multiple myeloma, monoclonal gammopathy of uncertain significance and polyclonal plasmacytosis.

AIMS: Differential diagnosis between multiple myeloma (MM), monoclonal gammopathy of uncertain significance (MGUS), and polyclonal plasmacytosis may be difficult in cases with not much bone marrow infiltration. Normal plasma cells express the antigens CD138, CD38, CD19, CD10 and D-related human leucocyte antigen (HLA-DR). Myelomatous plasma cells lack B lymphoid-associated markers and may express cell surface antigens associated with other haematopoietic lineages such as NCAM/CD56 (neural cell adhesion molecule). Recently, a monoclonal antibody, anti-CD56, has become available that can be used in fixed tissues embedded in paraffin, and it has been reported that osteoblastic cells of trabecular bone strongly express NCAM/CD56. METHODS AND RESULTS: We analysed NCAM molecule expression in 35 samples from patients with plasma cell disorders: 14 cases of MM, 16 cases of MGUS, and five cases of polyclonal plasmacytosis using immunohistochemistry in parallel in bone marrow core biopsies processed routinely and in bone marrow smears from the same patients. Of the MM samples 78% were CD56+ in smears and 92% positive in biopsies. We did not find strong CD56 expression in MGUS samples. One of five samples of polyclonal plasmacytosis was CD56+. A case was considered to be positive for CD56 expression if >50% of the CD138+ plasma cells expressed NCAM with an intensity on a par with that of the osteoblasts. CONCLUSION: We conclude that CD56 antibody is a very useful marker in the study of plasma cell proliferation in bone marrow biopsies and in bone marrow aspirates and is a great help in discriminating between MM, MGUS, and polyclonal plasmacytosis, especially in those cases with low infiltration.

Antibodies, Monoclonal↗
PubMed1995

[Lymphocytic plasma cell mastitis].

Plasma cell mastitis is a rare form of inflammatory, non-infectious, non-neoplastic, mastitis, not occurring during the post-partum and breastfeeding period. The pathogenesis of this lesion is not yet fully elucidated and an auto-immune origin is currently proposed. The common feature of this form of mastitis is the possibility of evolving towards recurrent aseptic abscesses. Treatment remains difficult and relapses are frequent with fistula formation to the skin, either spontaneously, or after surgery, even involving wide excision.

Adrenal Cortex Hormones↗
PubMed1991

Similar cytogenetic abnormalities in two cases of plasma cell leukemia.

Plasma cell leukemia (PCL) is a very rare disease. We report two cases of PCL with complex chromosomal abnormalities: long arm trisomy and short arm partial monosomy of chromosome 1, a marker derived from chromosome 8, and monosomy 13 were found in both cases; other additional chromosome abnormalities were also present in each case. Bastard et al. reports two similar cases in this issue. Cytogenetic studies in PCL have seldom been reported in the literature: chromosomal abnormalities are most often complex: chromosomes 1, 8, 11, 13, and 14 are those most frequently involved. Such cytogenetic findings are observed in advanced multiple myeloma. Cytogenetic, clinical, and immunological findings observed in PCL and the advanced stage of multiple myeloma are arguments for the single origin of pathogenesis.

Adult↗
PubMed2003

Increased expression of c-maf in pure red cell aplasia secondary to plasma cell dyscrasia.

Th2 dominancy in the peripheral T helper (Th) cell subsets were reported to be involved in the pathogenesis of pure red cell aplasia (PRCA). We encountered a PRCA case secondary to plasma cell dyscrasia that showed Th2 dominancy at the relapse of PRCA. Increased expression of c-maf, a transcriptional factor which induces Th2 differentiation of naive T-cells, and elevated expression of interleukin (IL)-4 were observed in the RNA derived from patient's bone marrow at relapse of PRCA. Following the administration of methylprednisolone which improved PRCA, normalization of Th1/Th2 ratio and decreased expression of c-maf and IL-4 were observed, which suggests that the upregulation of c-maf might have played a role in the pathogenesis of PRCA secondary to plasma cell dyscrasia.

Aged↗
PubMedDate not supplied

[Ca2+-transporting properties of myometrial plasma cell membrane Ca2+, Mg2+-ATPase reconstituted in liposomes].

Purified myometrium cells plasma membrane Ca2+, Mg(2+)-ATPase was reconstitute in liposomes in functionally active state by the method of cholate dialysis: it showed ATP-hydrolase activity increased by 0.8 microM A23187 average 4 times and it showed Mg2+, ATP-dependent Ca(2+)-transporting activity. Reconstituted system transported Ca2+ at an initial rate of 114.4 +/- 16.3 nmol.min-1.mg-1 with the stoichiometry Ca2+: ATP = 1: (3.2-3.7). Calmodulin increased by 30% the initial rate of Ca(2+)-accumulation by the proteoliposomes with reconstituted Ca2+, Mg(2+)-ATPase; 0.1 mM orthovanadate decreased by 80% Ca(2+)-accumulation by this system. Ca2+, Mg(2+)-ATPase reconstituted in liposomes is just Ca(2+)-transporting ATPase of the plasma membrane. Obtained enzyme preparate can be utilised for study of the properties of this important energy-dependent Ca(2+)-transporting system of smooth muscle cell.

Adenosine Triphosphate↗
PubMed2006

High affinity germinal center B cells are actively selected into the plasma cell compartment.

A hallmark of T cell-dependent immune responses is the progressive increase in the ability of serum antibodies to bind antigen and provide immune protection. Affinity maturation of the antibody response is thought to be connected with the preferential survival of germinal centre (GC) B cells that have acquired increased affinity for antigen via somatic hypermutation of their immunoglobulin genes. However, the mechanisms that drive affinity maturation remain obscure because of the difficulty in tracking the affinity-based selection of GC B cells and their differentiation into plasma cells. We describe a powerful new model that allows these processes to be followed as they occur in vivo. In contrast to evidence from in vitro systems, responding GC B cells do not undergo plasma cell differentiation stochastically. Rather, only GC B cells that have acquired high affinity for the immunizing antigen form plasma cells. Affinity maturation is therefore driven by a tightly controlled mechanism that ensures only antibodies with the greatest possibility of neutralizing foreign antigen are produced. Because the body can sustain only limited numbers of plasma cells, this "quality control" over plasma cell differentiation is likely critical for establishing effective humoral immunity.

Amino Acid Substitution↗
PubMed2000

Protective long-term antibody memory by antigen-driven and T help-dependent differentiation of long-lived memory B cells to short-lived plasma cells independent of secondary lymphoid organs.

Memory is a hallmark of immunity. Memory carried by antibodies is largely responsible for protection against reinfection with most known acutely lethal infectious agents and is the basis for most clinically successful vaccines. However, the nature of long-term B cell and antibody memory is still unclear. B cell memory was studied here after infection of mice with the rabies-like cytopathic vesicular stomatitis virus, the noncytopathic lymphocytic choriomeningitis virus (Armstrong and WE), and after immunization with various inert viral antigens inducing naive B cells to differentiate either to plasma cells or memory B cells in germinal centers of secondary lymphoid organs. The results show that in contrast to very low background levels against internal viral antigens, no significant neutralizing antibody memory was observed in the absence of antigen and suggest that memory B cells (i) are long-lived in the absence of antigen, nondividing, and relatively resistant to irradiation, and (ii) must be stimulated by antigen to differentiate to short-lived antibody-secreting plasma cells, a process that is also efficient in the bone marrow and always depends on radiosensitive, specific T help. Therefore, for vaccines to induce long-term protective antibody titers, they need to repeatedly provide, or continuously maintain, antigen in minimal quantities over a prolonged time period in secondary lymphoid organs or the bone marrow for sufficient numbers of long-lived memory B cells to mature to short-lived plasma cells.

Animals↗
PubMed2000

Activation of insulin-like growth factor I receptor signaling pathway is critical for mouse plasma cell tumor growth.

Plasma cell neoplasia in humans generally occurs as multiple myeloma, an incurable form of cancer. Tumors with marked similarity can be induced in mice by a variety of agents, including chemicals, silicone, and oncogene-containing retroviruses, suggesting the use of murine tumors as an informative model to study plasma cell disease. Herein, we have focused on the role of insulin-like growth factor I receptor (IGF-IR) signaling in the development of plasma cell disease. The insulin receptor substrate 2/phosphatidylinositol 3'-kinase/p70S6K pathway was found to be either constitutively or IGF-I-dependently activated in all plasma cell tumors. Biological relevance was demonstrated in that plasma cell lines with up-regulated IGF-IR expression levels exhibited mitogenic responses to IGF-I. More importantly, expression of a dominant-negative mutant of IGF-IR in these lines strongly suppressed tumorigenesis in vivo. Taken together, these results demonstrate that up-regulation and activation of IGF-IR and the downstream signaling pathway involving insulin receptor substrate 2, phosphatidylinositol 3'-kinase, and p70S6K may play an important role in the development of a broad spectrum of plasma cell tumors.

Animals↗
PubMed1987

Tp44 molecules involved in antigen-independent T cell activation are expressed on human plasma cells.

We have analyzed cells of the B lineage for expression of the Tp44 antigen, a 44,000 homodimer detected by monoclonal antibody 9.3 on approximately 80% of mature human T lymphocytes. Previous evidence has suggested that Tp44 may function as a receptor for accessory signals in T cell activation. High level Tp44 expression was observed on plasmacytomas grown in cell culture and on plasma cells from bone marrow biopsies of multiple myeloma patients. This antigen is not present on resting B cells from either peripheral blood or lymphoid organs, or on any other B cell tumor. The growth kinetics and Ig production in plasmacytomas are not affected by the binding of antibody 9.3. Moreover, the Tp44 molecule is co-expressed with PCA-1, an antigen characteristic of plasma cells, on peripheral blood B cells stimulated in vitro to differentiate toward plasma cells. Tp44 may represent a later stage of B cell differentiation than PCA-1 because unlike the PCA-1 antigen, this molecule could not be detected on any EBV-transformed cell line or Burkitt's lymphoma lines. The m.w. of the Tp44 molecule expressed on plasma cells and on T cells is identical, as determined by immunoprecipitation of radioiodinated cell surface proteins with monoclonal antibody 9.3. This antigen might be useful in studying the mechanism of growth and differentiation of human B cells, the heterogeneity within plasma cell populations, and B cell interactions with other components of the immune system.

Antibodies, Monoclonal↗
PubMedDate not supplied

The role of non-B cells in localizing an IgA plasma cell response in the intestine.

We have demonstrated previously that when autologous cells are re-infused into rats which had been primed via gut-associated lymphoid tissue (GALT) and given lumenal challenge, extravasation of IgA-committed plasma cell precursors in the intestinal lamina propria is an antigen-independent event, but their distribution after extravasation is influenced by the site of lumenal challenge. We report in this article, however, that when IgA plasma cell precursors are adoptively transferred from primed and challenged donors to syngeneic recipients given only lumenal challenge, localization in the intestinal lamina propria does not occur. This indicates that factors other than antigen are required for effective localization of IgA cells. The role of a cellular factor in directing their localization in the gut is demonstrated here by the ability of prior infusion of a B cell-depleted inoculum from immunized donors to encourage localization of adoptively transferred IgA cells in nonimmunized recipients. We suggest that T cells play a role in IgA plasma cell localization, possibly by producing a cytokine environment in the lamina propria conductive to maturation and/or proliferation of extravasated IgA plasma cell precursors.

Animals↗
PubMed1978

Polyclonal activation of human B lymphocytes in vitro by pokeweed mitogen: a simple technique for the simultaneous assessment of cell proliferation, generation of plasma cells, plaque-forming cells and immunoglobulin production.

A simple technique has been worked out for the simultaneous assessment of cell proliferation, generation of plasma cells, plaque-forming cells and immunoglobulin production from single cultures of 1 X 10(6) human peripheral blood lymphocytes stimulated with pokeweed mitogen (PWM). Kinetic studies showed that number of cells, thymidine incorporation rate, number of plaque-forming cells against fluorescein-isothiocyanate-haptenated sheep erythrocytes and concentration of IgM and IgG in the supernatant peaked on the average between day 5 and 7 of culture. This technique is particularly suitable for the analysis of hypogammaglobulinaemias in infancy.

Adult↗
PubMed1997

Effect of truncal vagotomy and capsaicin on mast cells and IgA-positive plasma cells in rat jejunal mucosa.

Immunocompetent cells, including mast cells and plasma cells (PC), in the intestinal mucosa are closely apposed to nerve fibres. Recent work has shown that vagal afferent nerves penetrate the jejunal mucosa and contact intestinal mucosal mast cells (IMMC); and that electrical stimulation of the vagus results in increased IMMC histamine content. To determine if the vagus nerve exerts a trophic effect on immunocompetent cells in the gut mucosa, the effects of truncal vagotomy and neonatal capsaicin treatment on IMMC and IgA containing PC in the lamina propria of rat jejunum were investigated. Three weeks after vagotomy, microdensitometric assessment of Alcian blue stained sections revealed 25% fewer IMMC in vagotomized animals than in controls (P < 0.05). Three months after neonatal capsaicin administration 28% fewer IMMC were found in treated rat jejunum, compared with littermate controls (P < 0.05). Three weeks post-surgery, IgA-PC densities were increased in both vagotomized animals (that also underwent pyloroplasty) and pyloroplasty controls, compared to animals subjected to laparotomy only. The proportion of lamina propria areas remained stable, indicating that the observations reflected real reductions in the numbers of IMMC. We also determined the densities of B-50 (a nerve growth-associated protein, also called GAP-43) immunoreactive nerve fibres in the lamina propria, as well as nerve profile areas, three weeks after vagotomy, and these parameters were unchanged. Taken together, these findings support the hypothesis that the vagus exerts a trophic effect on IMMC; and that capsaicin-sensitive nerves also affect the IMMC population. These data add to the growing body of evidence for a functional connection between IMMC and the nervous system.

Animals↗