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The Journal of Immunology, 2007, 178: 4726-4730.
Copyright © 2007 by The American Association of Immunologists, Inc.


CUTTING EDGE

Cutting Edge: B Cell Receptor (BCR) Cross-Talk: The IL-4-Induced Alternate Pathway for BCR Signaling Operates in Parallel with the Classical Pathway, Is Sensitive to Rottlerin, and Depends on Lyn1

Benchang Guo*, Derek Blair{dagger}, Thomas C. Chiles{dagger}, Clifford A. Lowell{ddagger} and Thomas L. Rothstein2,*

* Center for Oncology and Cell Biology, Feinstein Institute for Medical Research, Manhasset, NY 11030; {dagger} Department of Biology, Boston College, Chestnut Hill, MA 02467; and {ddagger} Department of Laboratory Medicine, University of California, San Francisco, CA 94143

B cell exposure to IL-4 alters subsequent BCR signaling such that ERK phosphorylation becomes signalosome-independent; however, the nature of this new, alternate signaling pathway and its relationship to the classical, signalosome-dependent signaling pathway are not known. In this study, we report that the alternate and classical pathways for BCR signaling are differentially affected by rottlerin, and by Go6976 or LY294002, respectively. Furthermore, in B cells lacking protein kinase C (PKC)beta, the classical pathway for BCR signaling is blocked, whereas the alternate pathway is little affected. Conversely, in B cells lacking Lyn, the alternate pathway for BCR signaling is blocked, whereas the classical pathway is little affected. The rottlerin-sensitive element is not PKC{delta}, inasmuch as the alternate pathway is not blocked in PKC{delta}-deficient B cells. These results indicate that the rottlerin-sensitive, Lyn-dependent alternate pathway, and the classical pathway, for BCR signaling operate in parallel when BCR engagement follows IL-4 exposure.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Public Health Service Grants AI40181, AI60896, and AI65495 awarded by the National Institutes of Health.

2 Address correspondence and reprint requests to Dr. Thomas L. Rothstein, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030. E-mail address: tr{at}nshs.edu

3 Abbreviations used in this paper: PLC, phospholipase C; PKC, protein kinase C; pERK, phosphorylated ERK; MZ, marginal zone.




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