PMID: 2494290Mar 1, 1989Paper

Isolation and characterization of a B lymphocyte mutant with altered signal transduction through its antigen receptor

The Journal of Experimental Medicine
J G MonroeN Sykes

Abstract

A receptor surface Ig (sIg) signaling variant of WEHI-231 was constructed to investigate components and linkages between various signaling events associated with signal transduction through sIg. Unlike the wildtype, crosslinking of sIgM on VS2.12-cl.2 did not result in downregulation of proliferation. Similarly, receptor crosslinking was uncoupled from inositol phospholipid (PI) hydrolysis and upregulation of c-fos expression in the variant. The signaling defect in VS2.12-cl.2 appears to be proximal to phospholipase C activation as direct G protein activation by A1F4- triggers PI hydrolysis and bypassing PI hydrolysis using phorbol diester stimulation of protein kinase C restores the inhibitable phenotype and the ability to upregulate c-fos. Even more interesting, sIg-linked Ca2+ responses by VS2.12-cl.2 are equivalent to these observed in the wildtype WEHI-231. These latter results suggest that contrary to current thought, sIg-generated signals may not be coupled to Ca2+ fluxes entirely via inositol phospholipid hydrolysis. Thus, VS2.12-cl.2 is a new and powerful tool with which to analyze signaling through sIg at the molecular level.

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Citations

Dec 1, 1989·Current Opinion in Immunology·L E Samelson
Aug 12, 1999·Molecular Immunology·J Jongstra-BilenJ Jongstra
Mar 1, 2002·Current Opinion in Immunology·Antonius G Rolink, Fritz Melchers
Feb 1, 1995·Immunology and Cell Biology·A R Gottschalk, J Quintáns
Mar 11, 2000·Immunology·L Tasker, S Marshall-Clarke
Apr 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·R H CarterD T Fearon
Oct 1, 1995·The Journal of Experimental Medicine·M TakataT Kurosaki
Apr 1, 1993·Immunological Reviews·E BaixerasC Martínez
Oct 23, 2002·Leukemia & Lymphoma·Bocoljub Ciric, Larry R Pease
Jun 1, 1991·Immunology Today·J E Alés-MartínezD W Scott
Oct 1, 1993·European Journal of Immunology·S MuthukkumarS Bondada
Aug 7, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·James B ChungJohn G Monroe
Dec 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Murali GururajanSubbarao Bondada
Sep 1, 1994·European Journal of Immunology·L E BenhamouP Sarthou
Jan 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J B ChungJ G Monroe

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