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Query: UMLS:C0220723 (PCA)
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Circulating monoclonal B cells in peripheral blood from patients with multiple myeloma or with monoclonal gammopathy of undetermined significance (MGUS) have previously been shown to express CD19, CD20, and PCA-1 and are predominantly CD45R0+, characterizing them as very late stage B cells. This work shows that the abnormal B cells are monoclonal as defined by their exclusive expression of either kappa or lambda light chain mRNA, and that the same type of light chain mRNA is expressed in both bone marrow plasma cells and blood B cells. These abnormal tumour-related circulating B cells express high densities of CD11b, a beta 2-integrin, which is expressed in a conformationally active state as defined by reactivity with monoclonal antibody 7E3. Normal peripheral blood B cells which do not bear CD11b acquire a high density after stimulation with pokeweed mitogen (PWM). At day 4 of culture, the expression of CD11b on normal CD19+ B cells was nearly comparable to that of the circulating myeloma late stage B cells. After PWM stimulation of circulating myeloma B cells the expression of CD11b was gradually lost during 4 days of culture, suggesting that its expression is dynamically regulated. Two patients with no phenotypically abnormal B cells in their blood at diagnosis acquired a large subset of CD11b+ B cells 4 weeks after initiation of chemotherapy. In most patients, a subset of the circulating myeloma B cells express a low density of CD5. The proportion of CD19+ B cells in the bone marrow expressing CD11b was much reduced compared with peripheral blood B cells, and CD11b was not detectable on plasma cells in the bone marrow, suggesting a sequential relationship of the B-cell subsets detected in our population of patients, involving gradual loss of CD11b concurrent with the loss of CD19 during B lineage differentiation. These cells appear to represent a continuously differentiating monoclonal B lineage culminating in the CD11b- plasma cell entrenched in the bone marrow. We speculate that the expression of conformationally active CD11b on the abnormal B cells in peripheral blood mononuclear cells of myeloma patients facilitates transendothelial migration of circulating myeloma B cells to the bone marrow.
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PMID:Restricted expression of immunoglobulin light chain mRNA and of the adhesion molecule CD11b on circulating monoclonal B lineage cells in peripheral blood of myeloma patients. 128 35

The origin of the malignant stem cell in multiple myeloma, despite years of investigation by many laboratories, remains elusive. We have described a population of monoclonal circulating B-lineage lymphocytes that has been detected in all myeloma patients analyzed, both at diagnosis and after chemotherapy, and that has many properties consistent with its definition as either a stem cell compartment or an intermediate between the stem cell and the bone marrow localized plasma cells. On average, 40% to 50% of peripheral blood mononuclear cells are abnormal B cells that express CD10 and PCA-1 in conjunction with B-lineage markers CD19, CD20, and CD24 and variable expression of CD5. The B cells are monoclonal by Southern blot analysis and represent a highly pleiomorphic population. The migratory patterns of these cells are unknown, and their presence in blood may reflect cells in transit from a parent organ such as spleen to bone marrow for terminal differentiation, or they may originate in the bone marrow prior to circulation and seeding of other skeletal or extraskeletal sites. The working hypothesis underlying this work postulates that these abnormal B cells originate outside the marrow, giving rise to plasma cells only after migration to the bone marrow, which provides a microenvironment conducive to terminal plasma cell differentiation. Bone marrow plasma cells do not include an actively proliferating component and are terminally differentiated end stage cells. In contrast, the circulating abnormal B cells include proliferating cells and appear to be heterogeneous in differentiation stage. Analysis of CD45 isoform expression indicates a population continuously differentiating from a late B-cell stage through the early plasma cell stages to an end stage plasma cell. Quantitative and qualitative expression of CD45 has been shown to characterize B-cell development, with a high density of the CD45RA isoform on mature resting B cells, a transition to CD45R0 on activated B cells, and a gradual loss of total CD45, predominantly of the CD45R0 isoform, during plasma cell development until, on end stage plasma cells, all CD45 expression is lost. In myeloma patients, all of these B-cell stages are represented, with the least differentiated B cells occurring in blood, intermediate stages in both blood and marrow, the most differentiated B and/or plasma cells in the bone marrow.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Monoclonal circulating B cells in multiple myeloma. A continuously differentiating, possibly invasive, population as defined by expression of CD45 isoforms and adhesion molecules. 153 57

The pathologic, immunologic, and clinical features of five cases of B-zone small lymphocytic lymphoma (BZSLL), characterized by a nondestructive growth pattern with a selective and complete replacement of the B-zone areas of lymph nodes, were examined. These findings were compared with those of 13 cases of intermediate differentiated lymphoma/mantle zone lymphoma (ILL/MZL) and 20 cases of typical small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). B-zone SLL was characterized histologically by a deceptively benign pattern at a low magnification, the lymph node architecture being substantially preserved, in contrast to the ILL/MZL and SLL/CLL cases, in which complete effacement of the normal architecture usually could be observed. Moreover, in BZSLL the cellular population was rather uniform and lacked either a prolymphocytic component or the small-cleaved lymphoid cells often seen in SLL/CLL and ILL/MZL cases, respectively. The phenotypic profile of the BZSLL clonal cell population studied by the immunoperoxidase method and by single- and double-labeling flow cytometric analyses (SIg+, CD19+, CD20+, CD21+, CD22+, CD24+, CD35+, CD37+, CD74+, CD45+, CD45R+, MB2+, HLA-DR+, Leu-8+, CD9+/-, CDw75+/-, CD5-/+, CD23-/+, CD10-, FMC7-, PCA-1-, CD25-, CD38-, CD43-, CD3-) appeared to be fairly homogeneous and sufficiently distinct from that of ILL/MZL, based on the absence of FMC7 and CD38 molecules, and from that of SLL/CLL due to significantly stronger expression of SIgs (P less than .05), the higher reactivity with anti-CD9 and -CD22 antibodies (P less than .05), the lower reactivity with anti-CD5 and -CD23 antibodies (P less than .05), and the absence of CD25 determinants. Several clinical features of patients with BZSLL, including age group, advanced stage disease, and high frequency of bone marrow and peripheral blood involvement, were similar to those found in the other patients with ILL/MZL and SLL/CLL, but none of the BZSLL patients had an absolute lymphocyte count higher than 15.0 x 10(9)/L at presentation. Based on the architectural pattern, cytologic features, immunophenotypes, and hematologic findings, we conclude that BZSLL is an unusual variant of SLL that is primary in the lymph nodes and should be distinguished from ILL/MZL and CLL.
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PMID:B-zone small lymphocytic lymphoma: a morphologic, immunophenotypic, and clinical study with comparison to "well-differentiated" lymphocytic disorders. 156 46

We investigated the origin of leukemic progenitors in a case of the simultaneous occurrence of myelomonocytic leukemia and multiple myeloma (IgG-kappa). At presentation, myeloperoxidase and nonspecific esterase-positive myelomonocytic cells had proliferated up to 12.2 x 10(9)/liter in the peripheral blood. Bone marrow cell differentials revealed the coexistence of myelomonocytic cells (30%) and atypical plasmacytoid cells (26%). Myelomonocytic cells in peripheral blood expressed both myeloid antigens (CD11b, CD13, CD14, CD15, CD33) and T/B-lymphoid antigens (CD2, CD4, CD5, CD7, CD10, PCA-1). Bone marrow mononuclear cells (BMMC) could be divided into PCA-1 strongly positive and PCA-1 weakly positive populations, which were considered to represent myeloma cells and myelomonocytic cells, respectively; the former were CD2-positive (CD2+), CD14-, and CD15-, whereas the latter were CD2+, CD14+, and CD15+. Immunohistochemical analysis revealed that, in addition to plasmacytoid cells, a minority of myelomonocytic cells showed a positive reaction for IgG staining, and production of IgG was observed in the culture supernatant of CD14+ myelomonocytic cells in peripheral blood. Southern blot analysis revealed the presence of two identical rearrangement bands of immunoglobulin heavy chain gene in both BMMC containing myeloma cells and myelomonocytic cells and CD14+ myelomonocytic cells in peripheral blood. In a long-term methylcellulose assay, peripheral blood mononuclear cells produced large compact colonies consisting of macrophages and IgG+ plasmacytoid cells (M phi/P colonies), while BMMC produced a different type of colonies consisting of CD14+ myelomonoblasts, macrophages, and IgG+ plasma cells (Mb/M phi/P colonies) in addition to M phi/P colonies. Recloning experiments showed that primary Mb/M phi/P colonies gave rise to both secondary M phi/P and Mb/M phi/P colonies. These observations strongly suggest that common leukemic progenitors provide both myeloma and myelomonocytic leukemia cells, and the mechanism of "lineage infidelity" is probably involved in the development of their "bilineal" differentiation.
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PMID:Simultaneous occurrence of myelomonocytic leukemia and multiple myeloma: involvement of common leukemic progenitors and their developmental abnormality of "lineage infidelity". 165 17

15 cases of HCL were studied with a panel of monoclonal antibodies against different leukocyte antigens. A B-cell phenotype different from that of B-CLL was observed (CD10-, CD19+, CD20+, CD21-, CD22+, CD37+, CD38-, FMC7+, LN1+, PCA-1+, BLy7+ and CD5-). As expected, CD11c and CD25 were positive and, in addition, a My7 and My9 positivity in varying degree was noted. 3 weeks of in vitro incubation did not significantly alter the phenotype. We conclude that HCL exhibits a unique phenotype among chronic B-cell leukemias, which is closer to the plasma cell stage of differentiation than that of B-CLL. The BLy7 monoclonal antibody seems to be a promising marker for HCL.
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PMID:Immunophenotype of hairy-cell leukemia. 222 30

B-chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease often expressed as a clonal expansion of CD5+ B cells. We report the characterization of CD5+ B cells from two unique B-CLL patients. Cells from patient 1 coexpressed CD5 (leu-1), CD19 (Leu-12), CD20 (B1), and HLA-DR; they were CD10 (J5), CD21 (B2), CD22 (Leu-14), CD25 (IL2-R1), PCA-1, surface, and cytoplasmic Ig negative. They suppressed normal peripheral blood lymphocyte (PBL) pokeweed mitogen (PWM) -stimulated immunoglobulin (Ig) synthesis greater than 80%. Cells from patient 2 were CD5 (Leu-1), CD19 (Leu-12), CD20 (B1), CD21 (B2), CD22 (Leu-14), HLA-DR, IgM, and kappa positive. They were negative for CD10 (J5), CD25 (IL2-R1), and PCA-1. These cells did not suppress normal PBL PWM-stimulated Ig synthesis but produced a monoclonal IgM kappa protein with rheumatoid factor-like activity. These observations suggest that there are different CD5+ B cell subsets, one immunosuppressive and the other autoreactive.
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PMID:CD5 positive immunoregulatory B cell subsets. 245 37

Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgM lambda, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgM lambda, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL.
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PMID:Monocytoid B-cell lymphoma: its evolution and relationship to other low-grade B-cell neoplasms. 278 62

We report a case of large granular lymphocytic leukaemia (LGLL) with mixed T-cell/B-cell phenotypes. The LGLL cells expressed T-cell markers such as CD1, CD2, CD3, CD5, CD7, CD8 and CD57. The CD8+ LGLL cells coexpressed B-cell markers including CD20 and PCA-1, and a fraction of purified CD8+ LGLL cells secreted double isotypes of immunoglobulins (IgG-kappa and IgA-kappa). Both TCRB and IGH genes were clonally rearranged. The LGLL cells could be divided into at least three subpopulations that were cytogenetically distinct, and all subpopulations involved the 11q23. The expression of both T- and B-cell markers on the LGLL cells suggests the involvement of a putative common lymphoid progenitor in leukaemic transformation.
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PMID:Large granular lymphocytic leukaemia with a mixed T-cell/B-cell phenotype. 948 15

Antigenic macromolecules present in food can induce inflammatory allergic reaction in sensitized persons. The aim of the present work is the development of an animal model to detect food antigens based on hypersensitivity reaction after food ingestion. New Zealand rabbits were divided in 5 groups. Group 1 (GI): control. G2: Ovalbumin (OVA) sensitized. G3: sensitized and orally challenged with OVA. G4: OVA sensitized and phosphate buffer solution challenged (PBS). G5: sensitized and challenged with OVA. Samples from cecum were stained with Alcian Blue pH < 1 for mast cells and with silver method for enteroendocrine cells (EEC). Other samples were immunostained with anti CD5 and CD25 monoclonal antibodies. Specific IgE levels were detected by PCA. Histopathology of G5 showed patchy edema, lymphangiectasia and eosinophilic infiltration. Results were expressed as cells per HPF (high power field); Mast cells in G1: 1.33; G2: 12.80 and G5: 10.20. Enteroendocrine cells in surface epithelium: G1: 1.6; G2: 6.0; G5: 4.2 and in deep epithelium: G1: 3.0; G2: 12.0 and G5: 7.3. Lymphocytes CD5+ in G1: 24.21: G2: 22.12 and G5: 23.97 and CD25+ in G1: 12.10: G2: 14.30 and G5: 21.68. Group 3 were similar to G1 and G4 to G2. We observed: mast cells increased in number probably due to OVA induced response. EEC showed an increase in sensitized animals because of higher expression of cytoplasmatic granules or differentiation from stem cells. Decrease in EEC number in challenged groups was likely to be based on vesicles release. Total T cells showed no significant differences among groups. CD 25+ cells were higher in sensitized and challenged animals. We concluded that rabbit model of sensitization and oral challenge is valid to study ingested food antigens and potential digestive pathologic reactions.
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PMID:[Biological model for detection of food antigens]. 1244 38