Biomedical subjects

G Bikah

Publications and source records attributed to G Bikah.

7 recordsLinked to original sources

PubMed2000

Role of CD5 in growth regulation of B-1 cells.

CD5 is a membrane glycoprotein that is expressed on a subset of B lymphocytes called B-1 cells, thymocytes and T cells. The CD5+ B-1 cells are normally unresponsive to surface Ig receptor induced growth signals unless the CD5 gene is deleted or sequestered away. Here we show that CD5 mediated negative regulation is unique to B cell receptor (BCR) signaling. The CD5 molecule in normal B-1 cells is constitutively tyrosine phosphorylated and associates specifically with SHP-1, an SH2 domain containing protein tyrosine phosphatase. CD5 promotes a prolonged interaction between BCR and SHP-1, which may be inhibitory to BCR signaling. CD5 was shown to modulate the function of autoantibody producing B cells in transgenic mice expressing anti-DNA antibodies.

Animals↗

PubMed2000

Regulating T helper cell immunity through antigen responsiveness and calcium entry.

We evaluated changes in the signaling potentials and proliferative capacity of single antigen-specific T helper (TH) cells during a primary immune response to a protein antigen. At the peak of cellular expansion in vivo all antigen-specific TH cells exhibited a profound block in CD3- and CD4-mediated mobilization of intracellular calcium together with a more global block in T cell receptor-independent capacitative calcium entry (CCE). The proliferative response of these antigen-specific TH cells to anti-CD3, anti-CD28 and IL-2 was also severely blunted. Cross-linking CD69 on a substantial fraction of CD69+ antigen-specific TH cells relieved this block in CCE and restored proliferative capacity in vitro. The CCE rescue operated through a CD69-coupled G protein and required calcium-bound calmodulin and calcineurin. These data reveal critical changes in the responsiveness of antigen-specific TH cells and provide evidence of new mechanisms for the regulation of antigen-specific TH cell development in vivo.

Animals↗

PubMed2000

Antigen-specific immunity. Th cell-dependent B cell responses.

Helper T cell-regulated B cell responses constitute a major component of the primary immune response to many pathogens. The subsequent development of antigen-specific immune memory is one critical outcome of this primary adaptive immune response. Antigen-specific immunity develops through a series of intercellular information exchanges organized around cognate T cell receptor-peptide/MHC interactions. Here, we discuss these complex molecularevents andtheircellularconsequences in a serial synapsis model of adaptive immunity. Our laboratory has developed strategies to isolate antigen-specific Th cells and B cells to analyze gene expression and cellular function in single responding lymphocytes directly ex vivo. These studies provide insight into the regulation and cellular organization of antigen-specific immune responses in vivo.

Animals↗

PubMed1999

Negative regulation of antigen receptor-mediated signaling by constitutive association of CD5 with the SHP-1 protein tyrosine phosphatase in B-1 B cells.

CD5, a membrane-associated glycoprotein, has been shown to negatively regulate antigen receptor-mediated growth responses in peritoneal B lymphocytes, thymocytes and mature T cells. The CD5-expressing peritoneal B cells (B-1) that are normally unresponsive to B cell receptor (BCR)-mediated growth signals mount a proliferative response to BCR cross-linking if the CD5 gene is deleted or if the CD5 molecule is sequestered away from the BCR. SHP-1, a cytosolic protein tyrosine phosphatase, has also been implicated in the negative regulation of antigen receptor-mediated signaling. The present study shows that SHP-1 is constitutively associated with the BCR in B-1 cells. This association is mediated in part by CD5, as it is reduced substantially after antigen receptor ligation in CD5(-/-) B-1 cells, and upon sequestration of CD5 from the antigen receptor complexes in wild-type B-1 cells. Prior cross-linking of CD5 also restores a normal calcium mobilization response as well as NF-kappaB activation in B-1 cells. These data support a model whereby CD5 negatively regulates antigen receptor-mediated growth signals by recruiting SHP-1 into the BCR complex in B-1 cells.

Animals↗

PubMed1998

A role for CD5 in cognate interactions between T cells and B cells, and identification of a novel ligand for CD5.

CD5 is a glycoprotein expressed at a high level on the surface of mature T lymphocytes. Studies with CD5 mAb and CD5-deficient mice have shown that the CD5 molecules have a significant role in T cell growth response. However, the precise role of CD5 in immune cell interactions is still unclear. The present study provides evidence that CD5 plays a direct role in providing growth signals during the contact-dependent activation and proliferation of splenic B cells. An anti-CD5 mAb inhibited Th1- and Th2-type cell-induced B cell proliferation. CD5-Ig, a chimeric fusion protein, induced proliferation of resting B cells. Flow cytometric analyses using CD5-Ig and mAb to CD72 demonstrated that CD5 bound to a ligand (CD5L), and this binding was not blocked by a variety of anti-CD72 mAb. Also, CD5-Ig did not bind to CD72+-transfected cells. Immunoprecipitation of surface labeled B cell molecules with CD5-Ig showed that CD5L was composed of 77-80 and 38-40 kDa polypeptide chains, distinct from CD72. CD5L was expressed on activated splenic B cells, but not T cells, whereas its expression was constitutive on peritoneal B cells and on B lymphoma cell lines.

Amino Acid Sequence↗

PubMed1996

CD5-mediated negative regulation of antigen receptor-induced growth signals in B-1 B cells.

A subset of B lymphocytes present primarily in the peritoneal and pleural cavities is defined by the expression of CD5 and is elevated in autoimmune diseases. Upon signaling through membrane immunoglobulin M (mIgM), splenic B lymphocytes (B-2) proliferate, whereas peritoneal B cells (B-1) undergo apoptosis. However, in CD5-deficient mice, B-1 cells responded to mIgM crosslinking by developing a resistance to apoptosis and entering the cell cycle. In wild-type B-1 cells, prevention of association between CD5 and mIgM rescued their growth response to mIgM crosslinking. Thus the B cell receptor-mediated signaling is negatively regulated by CD5 in normal B-1 cells.

Animals↗

PubMed1994

Cloning, sequencing, and expression of the Escherichia coli cytolethal distending toxin genes.

A limited number of Escherichia coli isolates which produce an apparently novel toxin, termed cytolethal distending toxin (CDT), have been reported. The toxic activity produced by these strains causes certain cultured cell lines to become slowly distended and then disintegrate. DNA was isolated from the CDT-producing E. coli strain, 9142-88, and cloned into a cosmid vector. Plasmid DNA from a toxin-positive transductant was further subcloned until a plasmid with a 4-kb insert which still encoded the toxin activity was obtained. Nucleotide sequencing of a portion of this insert revealed the presence of three adjacent open reading frames. Further subcloning and deletion analysis suggested that the products of all three open reading frames may be required for toxin activity. Minicell experiments identified the products of all three open reading frames. The three proteins had predicted sizes of 27,753,29,531, and 19,938 Da, and all three appeared to have strong consensus leader sequences. None of the three predicted proteins had significant homology to known proteins.

Amino Acid Sequence↗