Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study the capacity of early fetal B cells to produce Ig was investigated. It is shown that B cells from fetal liver, spleen, and bone marrow (BM) can be induced to produce IgM, IgG, IgG4, and IgE, but not IgA, in response to IL-4 in the presence of anti-CD40 mAb or cloned CD4+ T cells. Even splenic B cells from a human fetus of only 12 wk of gestation produced these Ig isotypes. IFN-alpha, IFN-gamma, and transforming growth factor-beta inhibited IL-4-induced IgE production in fetal B cells, as described for mature B cells. The majority of B cells in fetal spleen expressed CD5 and CD10 and greater than 99% of B cells in fetal BM were CD10+. Highly purified CD10+, CD19+ immature B cells and CD5+, CD19+ B cells could be induced to produce Ig, including IgG4 and IgE, in similar amounts as unseparated CD19+ B cells. Virtually all CD19+ cells still expressed CD10 after 12 days of culture. However, the IgE-producing cells at the end of the culture period were found in the CD19-,CD10- cell population, suggesting differentiation of CD19+,CD10+ B cells into CD19-,CD10- plasma cells. Pre-B cells are characterized by their lack of expression of surface IgM (sIgM). Only 30 to 40% of BM B cells expressed sIgM. However, in contrast to sIgM+,CD10+,CD19+ immature B cells, sorted sIgM-,CD10+,CD19+ pre-B cells failed to differentiate into Ig-secreting cells under the present culture conditions. Addition of IL-6 to these cultures was ineffective. Taken together, these results indicate that fetal CD5+ and CD10+ B cells are mature in their capacity to be induced to Ig isotype switching in vitro as soon as they express sIgM.
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PMID:Induction of isotype switching and Ig production by CD5+ and CD10+ human fetal B cells. 137 43

In an attempt to gain some insight into the many factors influencing antibody gene expression in human B cell lines, we have examined in detail the relationship between cell surface phenotype, cytokines, and the growth and antibody-producing capacity of a panel of immortalized human B cell lines. The cell panel comprised lines secreting either high or low titers of antibodies against Rhesus D, hepatitis B surface, and tetanus toxoid antigens. All the transformed cell lines exhibited a cell surface phenotype characteristic of well-differentiated peripheral blood cells strongly expressing CD23 and CD38 while weakly expressing CD10 and CD21. There was no obvious relationship between the antibody-body-secreting and proliferative capacity of the cell lines and their cell surface phenotype. Antibody secretion by the cells was rarely improved by the addition of a wide range of doses of recombinant IL-2, IL-4, or IL-6. In addition, such treatment frequently inhibited proliferation. Supernatants from some of the cell lines promoted the growth of unrelated cell lines but failed to influence antibody production. Such supernatants contained the highest concentration of IL-1, TNF beta, TGF beta, and soluble CD23. In contrast, the heterohybrid supernatant which inhibited cell growth secreted low levels of these cytokines. None of the cell lines secreted detectable amounts of IL-2, IL-4, INF gamma, or GCSF. There was no obvious relationship between cytokine production and antibody secretion. Finally, LPS had a slight but variable effect on antibody secretion but failed to influence cell growth.
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PMID:Cell surface phenotype, cytokines, and antibody gene expression in immortalized human B cell lines. 210 58

The EBV-transformed B cell line JR-2 proliferates in response to partially purified preparations of low m.w. B cell growth factor (LMW-BCGF). Two clones of JR-2 were generated that retained this LMW-BCGF responsiveness, exhibiting similar dose/response characteristics but differing phenotypically. The B10 clone grows as single, discrete, small round cells, whereas D3 grows in aggregates. The clones also differ in the expression of cell surface Ag, D3 being weakly DR+ and strongly CD23+, whereas B10 lacks these Ag. The CD23 on D3 cells binds IgE. Both clones are T9+, 4F2+, B1-, B2- and CALLA-. D3 expresses surface IgG and differentiates in the presence of LMW-BCGF, to secrete IgG. B10 lacks surface and cytoplasmic Ig and fails to differentiate in response to LMW-BCGF. CD23 cannot be induced on B10 by incubation with either LMW-BCGF or IL-4. B10 does not shed CD23 and shed CD23 is not a growth factor for either cloned line. Expression of CD23 on D3 cells is not affected by preincubation with LMW-BCGF. Neither B10 or D3 cells respond to rIL-1, rIL-2, rIL-4, rIL-6, rTNF-alpha/beta, rIFN-gamma, or to high m.w. BCGF (Namalwa), alone or in combination. Both clones absorb BCGF activity and crossover absorptions indicate that the clones remove growth factors required by each other. D3 and B10 both appear therefore to respond selectively to LMW-BCGF. These data suggest that the loss of CD23 from a cloned derivative of the cell line JR-2, although accompanied by considerable phenotypic change, is not associated with the disappearance of LMW-BCGF responsiveness, indicating that CD23 is not the essential receptor for LMW-BCGF.
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PMID:Low molecular weight B cell growth factor-responsive cloned human B cell lines. I. Phenotypic differences and lack of requirement for CD23 (Fc epsilon RII). 252 11

The effect of rIL-4 on the expression of low affinity receptor for the Fc part of IgE (Fc epsilon R2/CD23) and class II MHC antigens on Burkitt's lymphoma (BL) cell lines was investigated. Some of the BL lines contained low percentages of CD23 and HLA-DQ-positive cells, but virtually all cells expressed HLA-DR. IL-4 induced CD23 and class II MHC Ag expression on 7 of 9 BL. Optimal CD23 and class II MHC expression was observed after 48-72 h of incubation. Induction of CD23 and class II MHC Ag in the BL cell line BL2 by IL-4 was confirmed at the specific mRNA level. Significant activation of HLA-DQ mRNA was obtained after 6 h of incubation with IL-4 and gradually increased during prolonged incubation. Maximal induction of mRNA transcription occurred after 48 to 72 h. Optimal induction of HLA-DR and CD23 transcription in BL2 was also observed after 48 to 72 h. The induction of CD23 and class II MHC Ag seems to be specific for IL-4, because rIL-1, rIL-2, rIFN-gamma, recombinant granulocyte-macrophage-CSF, and a commercial source of low m.w. B cell growth factor were ineffective. In addition, the expression of class I MHC Ag, the transferrin receptor, CD38, CD25, CD10, CD20, and CD21 were not affected by IL-4. Interestingly, IFN-gamma and PGE2 suppressed the IL-4-induced membrane expression of CD23 and class II MHC Ag in a dose-dependent way. IFN-gamma also blocked IL-4-induced CD23 mRNA transcription in BL2 completely, whereas PGE2 (10(-7) M) was partially inhibitory. The induction of CD23 and class II MHC Ag by IL-4 required intact protein synthesis as shown by its inhibition by cycloheximide. These results indicate that the induction of CD23 and class II MHC Ag by IL-4 is regulated in a coordinated way.
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PMID:Regulation of Fc receptor for IgE (CD23) and class II MHC antigen expression on Burkitt's lymphoma cell lines by human IL-4 and IFN-gamma. 296 26

Two major B cell subpopulations were identified in the IgD- compartment of tonsils and subsequently isolated. They displayed the following phenotypes: CD10+CD38+CD44- (CD38+ B cells) and CD10-CD38-CD44+ (CD38- B cells). Of the CD38- B cells, 70% also expressed CD24 and CD39, whereas CD77 was specifically distributed on 40% of CD38+ B cells, suggesting an additional level of heterogeneity in the cellular composition of these two B cell types. Whereas the majority of CD38+ B cells were in cycle, most CD38- B cells were quiescent. Conversely, Bcl-2 was expressed in CD38- B cells but was not detected in CD38+ B cells. Of the CD38- B cells, 30% bore the homing receptor Leu-8/Mel-14, whereas CD38+ B cells lacked this marker. Thus, CD38- B cells have both survival capacity and migratory competence. Both subsets expressed surface (s) Igs which were mainly of the IgG class, implying that most of these cells have already undergone isotype switching. CD38- B cells proliferated vigorously and produced large amounts of IgG in response to cytokines, following ligation of slgs or CD40. In contrast, CD38+ B cells were only stimulated for DNA synthesis by a combination of IL-4 and anti-CD40 antibodies, and failed to differentiate into Ig-secreting cells regardless of the stimulus applied. We propose that CD38- B cells represent an extra-follicular mature B cell population which has been positively selected and rescued from apoptosis, whereas the CD38+ B cell subset is composed of germinal centre B cells.
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PMID:Phenotypic and functional heterogeneity of the IgD- B cell compartment: identification of two major tonsillar B cell subsets. 750 10

An in vitro culture system in which bone marrow-derived fibroblast-like cells support the growth of TdT+ colonies derived from CD34+/CD10- human bone marrow progenitor cells has recently been described. The regulatory role of cytokines during early B lineage commitment was investigated using this culture system. Expression of IL-7, a cytokine that induces proliferation of B cell precursors, was detectable in the adherent layer by PCR and bioassay. Lymphoid progenitor colonies were inhibited by neutralizing anti-IL-7 Ab, suggesting that IL-7 produced by the adherent layer was required even in the earliest recognizable stages of human B cell lymphopoiesis. IL-1 alpha, IL-4, and TNF-alpha inhibited lymphoid progenitor colonies in a dose-dependent fashion. Neutralizing Ab to IL-1 alpha, IL-4, or TNF-alpha did not increase lymphoid progenitor colonies, suggesting that inhibitory concentrations of these cytokines are not constitutively elaborated in the adherent layer. Recombinant Steel factor and IL-6 as well as neutralizing Abs to these cytokines did not significantly affect lymphoid progenitor colonies, arguing against an important role for these cytokines in early human B lymphopoiesis. These results indicate that IL-7 provided by the bone marrow microenvironment is a critical growth factor at the earliest recognizable stages of human lymphopoiesis. IL-1 alpha, IL-4, and TNF-alpha have been shown to indirectly stimulate release of myeloid growth factors. The inhibition of lymphopoiesis by these cytokines suggests a possible mechanism for the observed reciprocal relationship between lymphoid and myeloid supportive bone marrow microenvironments.
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PMID:Cytokine regulation of early human lymphopoiesis. 751 33

This study investigated the response of different CD5- B cell subsets to CD40 monoclonal antibody (mAb) in various combinations with interleukin (IL)-4 or rabbit anti-human mu chain antibody (a-mu-Ab). The different CD5- B cell subsets were isolated from tonsillar B cell suspensions depleted of CD5+ B cells and subsequently fractionated on Percoll density gradients. While resting CD5+ B cells proliferated and produced IgM molecules in response to a-mu-Ab, IL-4 and CD40 mAb as well as to Staphylococcus aureus Cowan strain I (SAC) and IL-2, resting CD5- B cells, which were co-purified in the same 60% Percoll fractions, consistently failed to respond. These cells were, however, activated by the stimuli employed, as demonstrated by their capacity to express the surface activation markers CD69, CD25 and CD71. Resting CD5+ B cells had the typical phenotype of mantle zone B cells (IgM+ IgD+ CD39+ CD38- CD10- CDw75dim), whereas resting CD5- B cells were CD38- CD39- CD10- CDw75 intermediate and expressed surface IgM but relatively little surface IgD and could not be classified as mantle zone or germinal center cells. The finding that purified germinal center cells (CD38+ CD10+ CD39- CDw75bright, IgG+) responded to CD40 mAb and IL-4 and also to SAC plus IL-2 further underlined the differences to resting CD5- B cells. However, some of the data collected suggest possible relationships between CD5- B cells and germinal center cells. The CD5- B cells isolated from the 50% Percoll fraction proliferated in response to a-mu-Ab, CD40 mAb and IL-4 as well as to SAC and IL-2. These cells had the same mantle zone B cell phenotype as the CD5+ B cells, but their capacity to respond to the stimuli in vitro was unrelated to a possible contamination with CD5+ B cells, as documented by the appropriate controls. Furthermore, upon exposure to SAC or phorbol esters, the large majority of CD5- B cells from the 50% Percoll fraction did not express surface CD5 and there was very little if any accumulation of CD5 mRNA. Finally, most of the cycling cells in the stimulated CD5- B cells did not express CD5. The CD5- B cells from the 50% Percoll fraction were comprised of a consistent proportion of cells that expressed surface activation markers.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Identification of two distinct CD5- B cell subsets from human tonsils with different responses to CD40 monoclonal antibody. 768 1

We have previously demonstrated that IL-7 can sustain the growth of normal human B cell precursors (BCP) for several weeks on bone marrow-derived stromal cells. Flow cytometric analysis of BCP recovered from IL-7 supplemented cultures revealed two- to threefold higher levels of cell surface CD19, compared with BCP maintained without IL-7. Short term culture of BCP showed that IL-7 enhancement of CD19 was dose-dependent, with increases detected by day 1 and plateauing by days 3 to 4. IL-7 increased cell-surface CD19 on small lymphoid cells, and to a greater degree on lymphoblasts, whereas cell-surface CD10 was unchanged. The CD34+/CD19+ pro-B cell population showed a greater increase in cell-surface CD19 compared with pre-B and immature B cells. IL-1, IL-3, IL-4, IL-6, and stem-cell factor had no effect on CD19. The potential functional significance of IL-7-enhanced cell-surface CD19 was examined using a F(ab')2 fragment of anti-CD19. This reagent had no effect on [3H]TdR incorporation in BCP cultured in the absence or presence of IL-7 for 5 days, but homotypic adhesion of BCP was induced at a concentration as low as 1.0 ng/ml F(ab')2 anti-CD19. IL-7 enhanced the F(ab')2 anti-CD19 induced homotypic adhesion of BCP in a dose-dependent manner. Blocking antibody studies indicated that members of the beta 1 or beta 2 integrin families did not mediate anti-CD19-induced homotypic adhesion, even though the adhesion was completely ablated by 10 mM EDTA. The pre-B and immature leukemic B cell lines NALM-6 and 1E8 expressed comparable levels of cell-surface CD19, and exhibited comparable increases after IL-7 stimulation. However, their homotypic adhesion responses to anti-CD19 were different. NALM-6 cells exhibited a strong homotypic adhesion response to anti-CD19 that was EDTA-resistant, and beta 1/beta 2 integrin independent. 1E8 cells only responded to anti-CD19 after IL-7 stimulation; this response was EDTA-sensitive and beta 1/beta 2 integrin independent. These collective results indicate that IL-7 not only acts as a growth factor for human BCP, but also regulates signal transduction through cell-surface CD19.
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PMID:Functional effect of IL-7-enhanced CD19 expression on human B cell precursors. 768 30

Light chain gene rearrangement during mammalian pre-B differentiation generally occurs in an orderly manner, beginning with kappa genes and proceeding through lambda genes. We have previously shown that human pre-B cell differentiation in vitro leads to a skewing toward lambda expression, resulting in a higher percentage of lambda+ cells than kappa+ cells. We now report that the multifunctional polypeptide transforming growth factor-beta (TGF-beta) exerts a selective inhibitory effect on the acquisition of cell surface lambda light chains during in vitro differentiation of normal human pre-B cells, giving rise to a balanced ratio (approximately 1:1) of kappa+ to lambda+ cells that resembles what normally exists in vivo. The TGF-beta effect was ablated using a neutralizing anti-TGF-beta antiserum and TGF-beta had no significant effect on the acquisition of kappa or surrogate light chains. Experiments using highly enriched pre-B cells (90-95% cytoplasmic mu+) suggested that the TGF-beta effect was directly on the pre-B cell or the pre-B cell to mu+/lambda+ immature B cell transition. The following peptides, cytokines, and antibodies had no effect on light chain acquisition or expression: substance P, vasoactive intestinal peptide, leu/met enkephalin, IL-1, IL-4, IL-7, anti-class II MHC, anti-CD24, anti-CD40, and the CD10 inhibitor phosphoramidon. A selective regulatory role for TGF-beta on normal human B cell development in the bone marrow microenvironment is suggested by these results.
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PMID:Transforming growth factor-beta regulates normal human pre-B cell differentiation. 815 4

Severe combined immunodeficient (SCID) mice were transplanted with different human fetal organs (SCID-hu mice), including thymus, liver, spleen, and omentum, and the serum levels of human IgM, IgG, IgE, and IgA were measured. In all SCID-hu mice significant levels (up to 590 ng/ml) of IgM were detected, irrespective of the organs transplanted. In contrast, IgG was present (up to 530 ng/ml) only when the fetal thymus was transplanted together with the fetal liver, indicating that the presence of human T cell is a prerequisite for in vivo isotypes switching by human B cells in SCID-hu mice. Additional transplantation of fetal spleen did not significantly increase IgG levels. was observed 4 months after transplantation. At that time, analysis by IEF showed that human IgG present in SCID-hu serum was at least oligoclonal. Furthermore, all IgG subclasses were represented in the human IgG pool. Human B cells were undetectable in the peripheral blood, spleen, and bone marrow of these SCID-hu mice; in contrast, B cells expressing CD19 could be isolated from the SCID-hu thymus. Considerable proportions of the CD19+ B cells coexpressed CD5, CD7, CD10, CD40, and CD2. These B cells spontaneously produced IgM and IgG in vitro and could be induced to switch to IgE-producing cells when cocultured with cloned activated CD4+ T cells in the presence of IL-4. Collectively, these data demonstrate that functionally mature B cells able to produce IgM and IgG in vivo, and IgE in vitro, are present in the SCID-hu human thymus.
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PMID:Human Ig production and isotype switching in severe combined immunodeficient-human mice. 832 22


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