Biomedical subjects

Georges Bismuth

Publications and source records attributed to Georges Bismuth.

22 records · Page 2Linked to original sources

PubMed2002

Human CD5 promotes B-cell survival through stimulation of autocrine IL-10 production.

CD5 is a negative regulator of B-cell receptor (BCR) signaling that is up-regulated after BCR stimulation and likely contributes to B-cell tolerance in vivo. However, CD5 is constitutively expressed on the B-1 subset of B cells. Contrary to CD5(-) B-2 B cells, B-1 B cells are long-lived because of autocrine interleukin-10 (IL-10) production through unknown mechanisms. We demonstrate herein a direct relationship between CD5 expression and IL-10 production. Human peripheral blood CD5(+) B cells produce more IL-10 than CD5(-) B cells after BCR activation. Introducing CD5 into CD5(-) B cells induces the production of IL-10 by activating its promoter and the synthesis of its mRNA. The cytoplasmic domain of CD5 is sufficient for this process. CD5 also protects normal human B cells from apoptosis after BCR stimulation while reducing the BCR-induced Ca(2+) response. We conclude that CD5 supports the survival of B cells by stimulating IL-10 production and by concurrently exerting negative feedback on BCR-induced signaling events that can promote cell death.

Apoptosis↗

PubMed2002

Controlling the immune system through semaphorins.

Semaphorins provide crucial attractive and repulsive cues involved in axon guidance. Several semaphorins have also been detected in cells of the immune system. Their influence on cell motility has been reported and is reminiscent of the biological function attributed to nervous system semaphorins. Receptors of the plexin and neuropilin family of proteins, also expressed by some immune cells, may be involved in semaphorin signaling in the immune system. However, semaphorins also affect the functioning of the immune system through receptors regulating lymphocyte activation. An important challenge in the future will be to determine whether, as in the nervous system, semaphorins help immune cells to establish connections with their appropriate targets.

Animals↗

PubMed2002

CD5-negative regulation of B cell receptor signaling pathways originates from tyrosine residue Y429 outside an immunoreceptor tyrosine-based inhibitory motif.

CD5 is a cell surface receptor that negatively regulates B cell function, but whose relationship to the immunoreceptor tyrosine-based inhibitory motif (ITIM) family of B cell inhibitory receptors is unclear. Using Fcgamma type IIB receptor-CD5 chimeras encompassing the cytoplasmic domain of CD5, we previously showed that a particular region of the molecule containing two tyrosine residues, Y429 and Y441, in an amino acid stretch similar to the Src autophosphorylation motif and a putative ITIM, respectively, antagonized early signaling events triggered through the B cell receptor (BCR). In this study, we provide evidences that only Y429 is mandatory for the inhibition by CD5 of the calcium response activated via the BCR. This residue also efficiently controls inhibition of the Ras/extracellular signal-related kinase-2 pathway. Analyzing the membrane translocation of the AKT protooncogene using its 3'-phosphoinositide-specific pleckstrin homology domain fused to the green fluorescent protein as a probe, we also show that CD5 strongly impairs its cellular redistribution and demonstrate the role played by Y429 in this process. We finally report that Y429 controls almost exclusively CD5 phosphorylation as well as inhibition of BCR-triggered IL-2 production upon coaggregation of the two receptors. Thus, CD5 uses an ITIM-independent strategy, centered on Y429, the major tyrosine-phosphorylated residue in its cytoplasmic domain, to inhibit BCR activation.

Amino Acid Motifs↗

PubMedDate not supplied

[The immunological synapse: models facing facts].

The notion of immunological synapse is generally associated to a concentric structure (a core of T cell receptors surrounded by a ring of adhesion molecules) often called "mature synapse". This schematic view has been built on observations corresponding to peculiar experimental conditions: very high antigen concentration presented by surrogate APCs such as lipid bilayers or B lymphoma. These observations have been hastily constituted in a dogma that a "normal" synapse should look like this, should form only in the presence of antigen, and should trigger a "stop" signal that completely immobilizes the T cell. However, when analyzing the interaction between naive T cells and dendritic cells (DC), that are the only antigen-presenting cells able to activate naive T cells, a very different picture emerges. Firstly, T-DC synapses can form in the absence of antigen; therefore antigen recognition is not a prerequisite for synapse formation. Secondly, these antigen-independent synapses are likely to play several roles, including sensitization of T cells for later antigen detection, and delivery of survival signals. Thirdly, in vivo, naive T cells interacting with antigen-laden DC do not fully stop, but start to make transient contacts with DCs for a few minutes, before continuing their exploration. It is only after several hours of this process that T cells eventually immobilize. Fourthly, the structure of the T-DC synapse is clearly multifocal, the two cells interacting through several tens of tight appositions of a few tens of nm in diameter. These numerous tight appositions are reminiscent of the microclusters that have been recently described at the T-bilayer interface. Finally, synaptic signaling is not a transient initial event, but is sustained for hours. In particular, sustained activation of phosphatidylinositol 3-kinase allows the exclusion out of the nucleus of FoxO transcription factors, normally maintaining T cells in a quiescent state.

Animals↗