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B Cell Receptor and BAFF Receptor Signaling Regulation of B Cell Homeostasis¹

Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136

B lymphocyte homeostasis depends on tonic and induced BCR signaling and receptors sensitive to trophic factors, such as B cell-activating factor receptor (BAFF-R or BR3) during development and maintenance. This review will discuss growing evidence suggesting that the signaling mechanisms that maintain B cell survival and metabolic fitness during selection at transitional stages and survival after maturation rely on cross-talk between BCR and BR3 signaling. Recent findings have also begun to unravel the molecular mechanisms underlying this crosstalk. In this review I also propose a model for regulating the amplitude of BCR signaling by a signal amplification loop downstream of the BCR involving Btk and NF-B that may facilitate BCR-dependent B cell survival as well as its functional coupling to BR3 for the growth and survival of B lymphocytes.

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 in part by National Institutes of Health AI060729 (to W.N.K.).

² Address correspondence and reprint requests to Dr. Wasif N. Khan, Department of Microbiology and Immunology, Miller School of Medicine, 1600 Northwest Tenth Avenue, 3147A Rosenstiel Medical Science Building, University of Miami, Miami, FL 33136. E-mail address: wnkhan{at}med.miami.edu

³ Abbreviations used in this paper: BAFF, B cell-activating factor; BR3, BAFF receptor; Btk, Bruton’s tyrosine kinase; DAG, diacylglycerol; Fo, follicular; int, intermediate; IKK, IB kinase; IP₃, inositol-1,4,5-triphosphate; LSM, lipid second messenger; MZ, marginal zone; PKC, protein kinase C; SLE, systemic lupus erythematosus; T1, early transitional type 1 (B cell); T2, late transitional type 2 (B cell); TACI, transmembrane activator and calcium-modulating/cyclophilin ligand-interacting protein.