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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

"T-cell B-cell Activating Molecule" (T-BAM) is an activation-induced surface protein on CD4+ T cells that mediates a contact-dependent signal for B cell differentiation and immunoglobulin (Ig) secretion. The T-BAM protein on a helper clone of Jurkat (D1.1) was affinity purified using the anti-T-BAM mAb, 5c8. The NH2-terminal amino acid sequence of purified T-BAM was determined and found to be highly homologous to the predicted NH2-terminal sequence of a T cell ligand to the B cell CD40 molecule (CD40-L). From a D1.1 cDNA library, a clone was isolated that encodes CD40-L by sequence and drives expression of T-BAM protein on transfected cells, demonstrating that the T-BAM and CD40-L genes and proteins are identical. Moreover, transfection of T-BAM was shown to confer to non-lymphoid cells, the ability to induce B cells to upregulate the expression of surface CD23 molecules. In previous studies we showed that T-BAM was expressed predominantly on activated CD4+ and on few if any CD8+ cells. Although the current work confirms that T-BAM is largely restricted to activated CD4+ T cells, we now provide definitive evidence that T-BAM can be expressed by a small population of CD8+ T cells after activation. Importantly, a subset of CD8+ T cells do not express T-BAM after activation and this T-BAM- phenotype is maintained on certain CD8+ T cell clones. Taken together, these data unify the biology and structure of T-BAM and CD40-L and this synthesis has implications for understanding the T cell regulation of the humoral immune response.
Mol Immunol 1994 Apr
PMID:Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: identity with the CD40-ligand. 751 69

In order to mount an effective antibody response to soluble and certain other types of antigens, B cells need help from T cells. Recently, an important receptor-ligand pair has been identified as essential for successful cognate interaction between these two classes of lymphocytes. CD40 was first identified as a receptor-like molecule on B cells which when ligated by antibody could deliver signals to prime for growth, differentiation, or survival. Later its counterstructure--termed CD40 ligand (CD40L)--was discovered to be an inducible type II glycoprotein of helper T cells. In this review, the central role of the CD40-CD40L interaction in the various phases of the B cell response to T-dependent antigens is discussed drawing from both in vitro and in vivo studies.
Cell Mol Biol (Noisy-le-grand) 1994
PMID:Central role of CD40 and its ligand in B lymphocyte responses to T-dependent antigens. 752 82

Germinal center (GC) B lymphocytes, defined by various criteria, have been shown to spontaneously undergo apoptosis in vitro unless they receive a positive signal. This rescue signal seems to be a multi-component process which involves not only the B cell receptor but also other cell surface receptors such as the CD40 antigen. In previous studies, we have shown that expression of the CD77 antigen is restricted to GC B lymphocytes and that CD77+ cells readily enter programmed cell death when cultured in vitro. In order to better characterize the CD77+ B lymphocytes, we have investigated the fate of these cells after rescue from apoptosis. Survival of CD77+ cells was achieved either with a combination of anti-CD40 mAb and IL4 (the CD40 system developed by Banchereau et al., (1991) Science 251, 70-72) or EBV infection. After 4 days of culture, similar phenotypic and functional changes of the CD77+ lymphocytes were observed in both systems: CD77 antigen was down-regulated, CD23 antigen which was originally negative became strongly expressed and the expression of CD38 and CD20 remained constant. Furthermore, large quantities of soluble CD23 were produced by the surviving cells. These results indicate that CD77 antigen is expressed by GC B cells which are highly susceptible to enter apoptosis but which are not doomed to die.
Mol Immunol 1995 Apr
PMID:The fate of human CD77+ germinal center B lymphocytes after rescue from apoptosis. 753 55

CD40 is a surface glycoprotein expressed on all human B lymphocytes and plays an important role in B-cell development, growth, and differentiation. Anti-CD40 monoclonal antibodies cause isotype switching in B cells treated with IL-4. CD40 is a member of a family of proteins that include low-affinity nerve growth factor receptor, TNF receptor, and the antigen Fas. The ligand for CD40 had been recently identified and has been assigned to the X chromosome. Using a panel of human-rodent somatic cell hybrids, we now show that CD40 maps to human chromosome 20.
Somat Cell Mol Genet 1993 May
PMID:Chromosomal localization of the gene for human B-cell antigen CD40. 768 85

Gene defects causing three X-linked human immunodeficiencies, agammaglobulinemia (XLA), hyper-IgM syndrome (HIGM), and X-linked severe combined immunodeficiency (SCID), have been identified. These represent the first human disease phenotypes associated with three gene families already recognized to be important in lymphocyte development and signaling: XLA is caused by mutations of a B-cell specific intracellular tyrosine kinase; HIGM by mutations in the tumor necrosis factor-related CD40 ligand, through which T cells deliver helper signals by direct contact with B-cell CD40; and SCID by mutations in the gamma chain of the lymphocyte receptor for interleukin-2. The great variety of patient mutations in all three genes represent both a challenge for genetic diagnosis and a resource for dissecting molecular domains and physiologic functions of the gene products.
Hum Mol Genet 1994
PMID:Molecular basis for three X-linked immune disorders. 784 38

The binding of CD40 ligand on activated T cells to CD40 on resting B cells induces the expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86). The induction of B7 molecules by CD40 ligand-CD40 interaction represents a critical step in rendering B cells competent for antigen presentation. The CBA/N mouse has a defect in CD40 signalling which has been attributed to a mutation in Bruton's tyrosine kinase. We have compared the ability of murine CD40 ligand to induce B7-1 and B7-2 expression on B cells isolated from CBA/N and wild-type CBA/J mice. We find that the CBA/N defect partially impairs both B7-1 and B7-2 induction via CD40. Subsequent experiments investigated the roles of different second messenger systems in B7-1 and B7-2 induction in normal B cells. In M12 B lymphomas either CD40 cross-linking or cAMP treatment can induce B7 molecules. Here we report that treatment with dibutyryl-cAMP also induces B7 molecules in normal B cells provided that they have been preactivated by CD40 cross-linking. We also find that PMA and ionomycin treatment of B cells induces B7-2 but not B7-1 expression. Our data therefore show roles for BTK, cAMP and PMA/ionomycin in B7 induction, as well as providing further evidence for differential regulation of B7-1 and B7-2 induction in B cells.
Mol Immunol 1996 Apr
PMID:Induction of costimulatory molecules B7-1 and B7-2 in murine B cells. the CBA/N mouse reveals a role for Bruton's tyrosine kinase in CD40-mediated B7 induction. 870 Jan 70

Interaction between CD40 on B cells and CD40 ligand (CD40L) on T cells has been shown to mediate T-cell contact help for B-cell proliferation, differentiation, and immunoglobulin isotype switching. It has recently been shown that cross-linking CD40 on mouse B cells induces germ line gamma1 and epsilon transcripts and that interleukin-4 synergizes with CD40 signaling to further induce these germ line transcripts. Germ line transcripts have been shown to be required for class switch recombination. Here we show that signaling via CD40 increases expression of a transiently transfected luciferase reporter plasmid driven by the germ line Cgamma1 promoter in M12.4.1 B-lymphoma cells. By linker-scanning mutation analysis of the promoter, we have identified a CD40-responsive region (CD40RR) which is able to confer inducibility by CD40L to a minimal c-fos promoter. The CD40RR contains three binding sites for NF-kappaB/Rel proteins which are each required for maximal induction of CD40RR activity by CD40L. Binding of the NF-kappaB/Rel proteins p50, p65, c-Rel, and RelB to the CD40RR is induced by CD40 signaling in M12.4.1 cells and in splenic B cells. Cotransfection of expression plasmids for p50 and p65 or p50 and RelB, but not c-Rel, into M12.4.1 cells transactivates the CD40RR and the germ line gamma1 promoter. These data demonstrate that NF-kappaB Rel proteins activated by CD40 ligation play an important role in induction of the germ line Cgamma1 promoter.
Mol Cell Biol 1996 Sep
PMID:Activation of NF-kappaB/Rel by CD40 engagement induces the mouse germ line immunoglobulin Cgamma1 promoter. 875 15

Interleukin-1 (IL-1) defines two polypeptides, IL-1 alpha and IL-1 beta, that possess a wide spectrum of biological effects. Two natural antagonists of IL-1 action have been characterized: the IL-1 receptor antagonist (IL-1Ra) and a soluble form of the type II IL-1 receptor. Neutralizing autoantibodies to IL-1 alpha have also been detected in sera of healthy individuals and patients with autoimmune or inflammatory diseases. To characterize such antibodies molecularly, we attempted to generate B cell clones producing anti-IL-1 alpha human monoclonal antibody (HuMAb) by combining Epstein-Barr virus-immortalization and CD40-activation of B lymphocytes from individuals with circulating anti-IL-1 alpha. We describe herein the generation and properties of a natural IgG4/kappa anti-IL-1 alpha monoclonal autoantibody, HuMAb X3, that bound specifically to human IL-1 alpha, but not to IL-1 beta and IL-1Ra, with a high affinity (Kd = 1.2 x 10(-10)M). HuMAb X3 inhibited IL-1 alpha binding to IL-1 receptors and neutralized biological activities of both recombinant and natural forms of IL-1 alpha. A recombinant form of HuMAb X3 was found to display identical specific IL-1 alpha antagonism. The presence of somatic mutations within X3 variable regions suggests an antigen-driven affinity maturation. This study extends the demonstration of the presence of high affinity neutralizing anti-IL-1 alpha autoantibodies that can function as a third type of IL-1 antagonist.
Mol Immunol
PMID:Generation and characterization of a human monoclonal autoantibody that acts as a high affinity interleukin-1 alpha specific inhibitor. 876 Feb 77

The Epstein-Barr virus (EBV) transforming protein LMP1 appears to be a constitutively activated tumor necrosis factor receptor (TNFR) on the basis of an intrinsic ability to aggregate in the plasma membrane and an association of its cytoplasmic carboxyl terminus (CT) with TNFR-associated factors (TRAFs). We now show that in EBV-transformed B lymphocytes most of TRAF1 or TRAF3 and 5% of TRAF2 are associated with LMP1 and that most of LMP1 is associated with TRAF1 or TRAF3. TRAF1, TRAF2, and TRAF3 bind to a single site in the LMP1 CT corresponding to amino acids (aa) 199 to 214, within a domain which is important for B-lymphocyte growth transformation (aa 187 to 231). Further deletional and alanine mutagenesis analyses and comparison with TRAF binding sequences in CD40, in CD30, and in the LMP1 of other lymphycryptoviruses provide the first evidence that PXQXT/S is a core TRAF binding motif. The negative effects of point mutations in the LMP1(1-231) core TRAF binding motif on TRAF binding and NF-kappaB activation genetically link the TRAFs to LMP1(1-231)-mediated NF-kappaB activation. NF-kappaB activation by LMP1(1-231) is likely to be mediated by TRAF1/TRAF2 heteroaggregates since TRAF1 is unique among the TRAFs in coactivating NF-kappaB with LMP1(1-231), a TRAF2 dominant-negative mutant can block LMP1(1-231)-mediated NF-kappaB activation as well as TRAF1 coactivation, and 30% of TRAF2 is associated with TRAF1 in EBV-transformed B cells. TRAF3 is a negative modulator of LMP1(1-231)-mediated NF-kappaB activation. Surprisingly, TRAF1, -2, or -3 does not interact with the terminal LMP1 CT aa 333 to 386 which can independently mediate NF-kappaB activation. The constitutive association of TRAFs with LMP1 through the aa 187 to 231 domain which is important in NF-kappaB activation and primary B-lymphocyte growth transformation implicates TRAF aggregation in LMP1 signaling.
Mol Cell Biol 1996 Dec
PMID:Association of TRAF1, TRAF2, and TRAF3 with an Epstein-Barr virus LMP1 domain important for B-lymphocyte transformation: role in NF-kappaB activation. 894 65

Germline epsilon (I epsilon) transcription is requisite for IgE switch recombination. I epsilon transcription is markedly increased by ligation of CD40 and/or by IL-4 stimulation. By contrast, we found previously that stimulation through CD30 inhibits I epsilon transcription in EBV-transformed B cell lines. To characterize the molecular mechanisms involved in these contradictory events, the promoter elements that are responsible for I epsilon transcriptional regulation were determined using stable CAT reporter gene constructs. The results define a 95 bp CD30 responsive element (CD30RE) located 5' of the previously defined CD40 responsive element (CD40RE) that resides within the same 95 bp fragment as the IL-4RE and ablates CD40L induced I epsilon promoter activity. However, IL-4 overrides the inhibitory effect of CD30L. These results define a CD30RE and provide further evidence for the complex regulation of I epsilon transcription by various members of the CD40L/TNF alpha family of molecules.
Mol Immunol 1996 Aug
PMID:A CD30 responsive element in the germline epsilon promoter that is distinct from and inhibitory to the CD40 response element. 896 Jan 21


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