Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pre-B cell lines proliferating for several months on stromal cells in the presence of interleukin 7 (IL-7) were established from fetal liver of (NZB x NZW)F1 mice. They express the B lineage-specific markers PB76, B220, and VpreB, but do not express surface immunoglobulin (sIg). Upon removal of IL-7 from the culture, they differentiate to sIg+ B cells that can then be stimulated by lipopolysaccharide to become IgM-secreting cells. Transfer of these pre-B cell lines into SCID mice leads to hypergammaglobulinemia of IgM (600-900 micrograms/ml), IgG2a (1-3 mg/ml), and IgG3 (300-500 micrograms/ml) for the next 3-5 mo. The spleen appears populated with (NZB x NZW)F1-derived pre-B cells, few B cells, and many IgM and/or IgG-producing plasma cells. In contrast, SCID mice populated with pre-B cell lines of normal (C57BL/6 x DBA/2)F1 mouse fetal liver develop normal levels of serum IgM (approximately 100-300 micrograms/ml), almost no detectable levels of IgG, and no plasma cell hyperplasia. The (NZB x NZW)F1 pre-B cell-populated SCID mice contain elevated serum titers of IgG antinuclear autoantibodies, but no retroviral gp70-specific nor erythrocyte-specific autoantibodies. Up to 20% of the SCID mice develop proteinuria as a consequence of IgG deposits in the kidney glomeruli during a 7-mo period of observation. All signs of autoimmune disease seen in these mice are independent of the sex of the SCID host. This experimental system provides a distinction between the disease-determining (NZB x NZW)F1 genes, which are expressed in the B lymphocyte lineage and cause the development of the disease, from those expressed in other cell lineages which only modulate its progression.
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PMID:Development of autoimmune disease in SCID mice populated with long-term "in vitro" proliferating (NZB x NZW)F1 pre-B cells. 140 80

We have demonstrated that CD45, a receptor-type protein tyrosine phosphatase, selectively regulates IgG production at the generative phase of precursors of IgG producers whereas Lyb-2 regulates IgG1 production induced by IL-4 in lipopolysaccharide (LPS)-activated B cells by acting on the generation of IgG1 precursor cells. These results point to an interesting possibility that both CD45 and Lyb-2 mediate a critical regulatory step(s) in IgG class switching. The present study was conducted to examine this possibility by elucidating the molecular mechanisms whereby CD45 and Lyb-2 control IgG synthesis in B cells activated by LPS and IL-4. Northern blot analysis showed that steady-state levels of C gamma 3, C gamma 2b and C gamma 1, but not Cmu, mRNA in LPS-activated B cells were reduced approximately 3- to 5-fold by CD45 mAb, and that the C gamma 1 mRNA level in B cells activated by LPS and IL-4 was significantly decreased by Lyb-2 mAb and CD45 mAb. Further, CD45 mAb inhibited expression of germline gamma 2b and gamma 3 transcripts induced by LPS and germline gamma 1 transcript expression induced by IL-4 plus LPS, but caused no inhibition in IL-4-induced germline gamma 1 transcript expression. In contrast, Lyb-2 mAb did not exert any inhibitory effect on the generation of germline gamma 1 transcripts induced by IL-4 and LPS or by IL-4 alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of lipopolysaccharide- and IL-4-induced immunoglobulin heavy chain gene activation: differential roles for CD45 and Lyb-2. 153 9

The B220 cell marker is expressed on B cells and on T cell precursors. In order to determine the involvement of the B220 antigen on murine lymphoid differentiation, we treated 5-10-week-old mice periodically with a specific anti-B220 antibody, RA3-6B2, a non-cytolytic IgG2b. After the third injection, a significant reduction (P less than 0.02) in the number of thymocytes and less dramatically in the number of splenocytes was observed. This reduction was predominantly due to a decrease of cells carrying the following markers: Thy-1.2+, Lyt-1+, Lyt-2.3+, L3T4+, and asGM1+. Mitogenic response to concanavalin A, phytohaemagglutinin and lipopolysaccharide, mixed lymphocyte reaction, cytotoxic T cell activity, and plaque-forming cell generation were significantly decreased after the treatment (P less than 0.01). These results show that the in vivo treatment with anti-B220 monoclonal antibody reduced the number of T and B cells and modified their functional activity. This suggests that the B220 antigen is involved in the maturation of both T and B cells.
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PMID:In vivo treatment with anti B-220 monoclonal antibody affects T and B cell differentiation. 169 18

Anti-Ig stimulated murine B cells express high levels of surface CD5 (ly-1) and increased CD44 while maintaining surface IgD, CD23 and J11d. Sorting of CD5- and CD5+ cells demonstrates that anti-Ig induces CD5 expression rather than the selective expansion of CD5+ cells. Anti Ig plus interleukin-6 (IL-6) induces the CD23, IgD, low ly-5 (B220) (CD45low), J11dhigh phenotype of typical CD5+ peritoneal B cells. In contrast, lipopolysaccharide (LPS)-stimulated B cells have high levels of CD44 but decreased surface IgD, CD23 and J11d and no CD5. Thus LPS and anti-Ig generate activated cells with differing phenotypes. Induced CD5+ cells have increased viability, even in the absence of added exogenous factors, while the viability of CD5- B cells is dependent on factors such as IL-4. We conclude that conventional CD5- B cells can be activated by either of two pathways: one generating CD5+ B cells; the other yielding conventional activated cells. We hypothesize that the first path requires slg cross-linking and corresponds to T-independent (type 2) stimulation, while cognate interaction with helper T cells in the absence of slg cross-linking induces B cells to enter the second path.
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PMID:Treatment of murine CD5- B cells with anti-Ig, but not LPS, induces surface CD5: two B-cell activation pathways. 171 72

We characterized the basis for the follicular lymphoproliferation in transgenic mice bearing a Bcl-2-immunoglobulin (Bcl-2-Ig) minigene representing the t(14;18) of human follicular lymphoma. Discriminatory S1 nuclease protection assays revealed that the Bcl-2-Ig transgene was overexpressed relative to endogenous mouse Bcl-2 in spleen and thymus. Western (immunoblot) analysis demonstrated the overproduction of the human 25-kilodalton Bcl-2 protein, which arose from the transgene, in spleen, thymus, and the expanded B-cell subset. Despite the generalized lymphoid pattern of deregulation, two-color flow cytometry and density gradient centrifugation indicated that the expanded lymphocytes were predominantly small, resting B cells coexpressing B220, immunoglobulin M (IgM), IgD, Ia, and kappa. Cell cycle analysis confirmed that about 97% of these expanded B cells reside in G0/G1. An extensive characterization of transgenic lines revealed a fourfold excess of IgM-IgD-expressing B cells in spleen and dramatically increased numbers in bone marrow. While resting, these cells proliferated in response to lipopolysaccharide and anti-IgM and demonstrated normal B-cell colony formation in soft agar. Moreover, these B cells, which demonstrated an extended survival in vitro even in the absence of stroma, were also resting in G0, yet were capable of proliferative responses. These findings provide consistent evidence that the accumulation of B cells after Bcl-2 overproduction is secondary to prolonged cell survival and not increased cell cycling. This suggests a unique role for Bcl-2 as a proto-oncogene that enhances cell survival independent of promoting cell division.
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PMID:Deregulated Bcl-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M and D-expressing B-cell population. 218 11

We have isolated and characterized a new series of B lymphoma which occurred spontaneously in a group of CBA/N mice that were transferred with spleen or lymph node cells from 24-month-old CBA/Ca mice. Tumor cell lines from six CBA/N mice that received spleen cells were rescued and designated as BKS-2, BKS-3, BKS-4, BKS-5, BKS-6, and BKS-7. Also, tumor cells from a recipient of lymph node cells were rescued and the resulting cell line was designated BKL. These tumor cells expressed membrane immunoglobulin (mu, kappa), major histocompatibility complex Class I and Class II molecules, B220, Lyb8, Fc receptors, J11d, interleukin 2 receptors, and Ly1. All of the tumors did not express the T cell specific markers Thy 1.2, L3T4, and Lyt2.1. They appeared to be clonal in origin, since they exhibited common rearrangements at both heavy and light chain immunoglobulin loci. Phenotypically, these lymphomas appeared to be analogous to immature B cells. Also, these lymphomas displayed different functional reactivities when treated with various B cell mitogens and growth factors in vitro. Anti-mu antibodies which normally induce B cell growth inhibited the proliferation of these lymphoma cells in vitro, whereas they responded to lipopolysaccharide, T cell-derived growth factors, and interleukin 5 by enhanced proliferation. These tumor cells expressed constitutively high levels of c-myc mRNA.
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PMID:Isolation and immunological characterization of a group of new B lymphomas from CBA mice. 264 95

Splenic B cells of A/J mice immunized with 2,4,6-trinitrophenyl (TNP)-lipopolysaccharide were fused with 2.52M, a mutant of a B cell line, in the presence of polyethylene glycol and dimethyl sulfoxide. TP67.21, a subclone of a resulting hybridoma, expresses IAk, IEk, IgM, B220, P50, and receptors for C3 fragment of complement, the Fc portion of IgG, and interleukin 2 receptor on the cell membrane; it also possesses receptor molecules for TNP on its surface, derived from TNP-reactive B cells of A/J mice primed with TNP-lipopolysaccharide used for somatic hybridization, by a rosette-forming assay with TNP-sheep erythrocytes. In contrast, parental 2.52M lacks IAk and IEk on the cell membrane and does not bind to TNP-sheep erythrocytes under the same conditions. Thus, it is likely that TP67.21 is an antigen-specific B cell clone directed against TNP. The antigen binding of cells was markedly inhibited by the specific free hapten or anti-IgM antibodies. Interestingly, TP67.21 was induced to generate a significant amount of anti-TNP antibody when treated with TNP conjugates including T cell-independent and -dependent antigens, such as TNP-lipopolysaccharide, TNP-bovine serum albumin, TNP-ovalbumin, and TNP-keyhole limpet hemocyanine in the absence of T cell help, as well as polyclonal activators; this was followed by a marked decrease in the expression of B cell surface markers on the cell membrane. This suggests that the cross-linkage of receptor molecules on TP67.21 by antigen may directly provide a differentiative signal for maturation to a lineage of B cells, and consequently results in the generation of antigen-specific antibodies without T cell involvement.
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PMID:Establishment of an antigen-specific B cell clone by somatic hybridization. 282 Nov 18

The effect of fractionated total lymphoid irradiation (TLI) on the induction of cells blocking in vivo B cell maturation was examined. (BALB/c x C57BL/6)F1 mice received 200 rds lymphoid irradiation daily for 8 days. One month after termination of the irradiation splenic T cells of TLI-treated mice were transferred, together with normal bone marrow cells, to lethally irradiated hosts. In addition, splenic cells or splenic B cells of TLI mice were transferred to irradiated hosts. Two months later, we checked the reconstituted mice for their ability to produce in vivo anti-trinitrophenyl (TNP)-Ficoll antibodies and their capacity to respond in vitro to dextran sulfate and lipopolysaccharide. In parallel, stained spleen cells were analyzed on the fluorescence-activated cells sorter using monoclonal anti-mu, anti-delta and anti-B220 surface marker antibodies. The results indicate that splenic T cells originating from TLI-treated mice cause maturation arrest of normal and TLI-treated B cells, since normal bone marrow cells injected together with those cells have immature phenotypic and functional features. In addition, neither splenic cells nor splenic B cells of TLI-treated mice can mature upon transfer to normal irradiated hosts. The B cells are IgM+, IgD-; they respond with a high proliferation rate to dextran sulfate and low proliferation rate to lipopolysaccharide, and poorly to TNP-Ficoll challenge.
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PMID:In vivo blockage of B cell maturation by splenic T cells of total lymphoid irradiated mice. 661 Dec 67

Clones and lines of precursor (pre) B cells can be established by limiting dilutions of unseparated cell suspensions of fetal liver or bone marrow on stromal cells in the presence of interleukin (IL)-7. When IL-3 is used instead of IL-7, cultures are regularly overgrown by different precursor cells of the myeloid lineage, as well as by adherent cells that inhibit pre-B-cell expansion. However, in the presence of either IL-7 or IL-3, clones of pre-B cells can be established on stroma cells at frequencies near one in one when the cultures are initiated with cell sorter purified CD45RO (B220)+/c-kit+ fetal liver or bone marrow derived pre-B cells. Clones grown on stromal cells in the presence of IL-7 can be regrown in IL-3, and vice versa. Pre-B cells that proliferate on stromal cells in the presence of IL-7 or IL-3 have the same phenotype, ie, are B220+ c-kit+, CD43+, and surrogate light chain+. Removal of the growth factors (IL-7, respectively IL-3) from the cultures results in differentiation to surface immunoglobulin (slg) positive, c-kit-, CD43-, surrogate light chain- B cells, a fraction of which is lipopolysaccharide (LPS) responsive as shown by IgM secretion. These results show that IL-7 and IL-3 stimulate largely overlapping populations of precursor B cells from bone marrow to proliferate for long periods of time in the presence of stromal cells. Thus, IL-7 and IL-3 are alternative growth factors for the same pre-BI cell.
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PMID:Interleukin-3 and interleukin-7 are alternative growth factors for the same B-cell precursors in the mouse. 753 88

The effect of BTS 71 412, 4-acetyl-1-(4-chlorophenyl)-3-(2-methylthiophenyl)- 3-pyrazolin-5-one, has been determined on a variety of immune reactions in vitro in order to gain a further insight into the mechanisms whereby this novel immunosuppressive drug suppresses cell and antibody mediated immune responses in vivo. BTS 71 412 markedly inhibited [3H]thymidine incorporation by mouse splenocytes activated with concanavalin-A (IC50 = 20.1 microM), phytohaemagglutinin (IC50 = 4.6 microM), lipopolysaccharide (LPS) (IC50 = 3.2 microM), anti-IgM (mu-chain specific) (IC50 = 2.6 microM), or mixed lymphocyte culture (IC50 = 8.4 microM). Activity of BTS 71 412 was not associated with a reduction in cell viability. BTS 71 412 also prevented [3H]thymidine incorporation by the murine HT-2 helper T-cell clone when cultured with IL-2 (IC50 = 7.6 microM) or IL-4 (IC50 = 7.3 microM), enriched Thy-1+ T-lymphocytes stimulated with phorbol 12-myristate 13-acetate plus ionomycin (IC50 = 3.6 microM), and enriched B220- B-lymphocytes stimulated with LPS (IC50 = 3.0 microM). Splenocytes cultured with BTS 71 412 produced lower levels of interleukin (IL)-2, IL-10 and interferon-gamma when stimulated with concanavalin-A (IC50 values 42 microM, 22 microM and 60 microM, respectively). The compound suppressed in vitro antibody responses to keyhole limpet haemocyanin (IC50 = 2.3 microM), but did not reproducibly inhibit IL-6 or tumour necrosis factor alpha production by adherent peritoneal macrophages stimulated with LPS in vitro. These data indicate that BTS 71 412 specifically inhibits both B- and T-lymphocyte activation and proliferation but does not affect macrophage activation in vitro.
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PMID:BTS 71 412: in vitro profile of a novel pyrazolinone immunosuppressant. 759 59


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