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001-es BibID:	BIBFORM054325
035-os BibID:	PMID: 9052860
Első szerző:	Sármay Gabriella
Cím:	Integration of activatory and inhibitory signals in human B-cells / Gabriella Sármay, Gábor Koncz, János Gergely
Dátum:	1996
ISSN:	0165-2478
Megjegyzések:	Fc gamma receptors type IIb1 (Fc gamma RIIb1) inhibit B-cell activation when co-ligated with B-cell antigen receptors (BCR) by immune complexes. In murine B-cells the inhibition is mediated by the interaction of the phosphorylated immunoreceptor tyrosine-based inhibitory motif (P-ITIM) of Fc gamma RIIb1 with the SH2 domain containing protein tyrosine phosphatase, SHP1. To clarify the mechanism of Fc gamma RIIb mediated inhibition of human B-cells we have studied the association of signaling molecules with human Fc gamma RIIb1 after co-ligating with BCR. Fc gamma RIIb1 were affinity purified from the Burkitt lymphoma cell line, BL41. Several tyrosine phosphorylated proteins were co-isolated with Fc gamma RIIb1 at 145, 110, and 50-60 kDa, which were not present in Fc gamma RIIb1 free immune complexes. Among these molecules we have identified the p52 She adaptor protein. Furthermore, we have shown that the insolubilised synthetic peptide corresponding P-ITIM bound She, Lyn and the p75 and p110 unidentified tyrosine phosphorylated proteins. Here we describe that the cell membrane associated She is partially dephosphorylated in BCR-Fc gamma RIIb1 co-ligated samples, suggesting that its function in regulating p21ras monomeric G protein is impaired. Indeed, we have detected a lower p21ras activity in BCR-Fc gamma RIIb1 co-crosslinked samples. These data indicate that co-ligation of BCR and Fc gamma RIIb1 interrupts signal transduction between protein tyrosine kinase activation and p21ras mediated activation pathway. Since in contrast to the mouse B-cells both Fc gamma RIIb1 and Fc gamma RIIb2 are expressed in human B-cells, we have investigated the inhibitory function of the two receptors in Fc gamma RIIb negative Burkitt lymphoma cell line ST486 transfected with Fc gamma RIIb1 and Fc gamma RIIb2, respectively. Both Fc gamma RIIb1 and Fc gamma RIIb2 inhibited the rise of intracellular Ca2+ induced by the crosslinking of BCR. The rate of the inhibition depended on the ratio of the co-crosslinked receptors (BCR-Fc gamma RIIb1) to the crosslinked BCR (BCR-BCR). Co-crosslinking of the two receptors inhibited not only the capacitive Ca2+ entry but rather the total Ca2+ response in both Fc gamma RIIb1 and Fc gamma RIIb2 transfected human B-cells. CD19 represents the signal transduction unit of complement receptor, CR2 (CD21), and is responsible for the complement activating IgM-immune complex induced enhancement of B-cell activation. Co-crosslinking of CD19 and BCR was shown to enhance B-cell activation due to the recruitment of further signaling molecules to the activator complex by the phosphorylated tyrosine residues of CD19. Here we show a novel finding that co-ligation of CD19 with Fc gamma RIIb1 inhibits the CD19-induced upregulation of Ca2+ response. The results indicate that IgG plus complement containing immune complexes may inhibit B-cell activation in vivo, due to the Fc gamma RIIb1-mediated interruption of signal transduction via both BCR and CD19.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Fc gamma RIIb human B-cells regulation signal transduction
Megjelenés:	Immunology Letters. - 54 : 2-3 (1996), p. 93-100. -
További szerzők:	Koncz Gábor (1970-) (biológus, immunológus) Gergely János
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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