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Vav Proteins Regulate the Plasma Cell Program and Secretory Ig Production¹

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

Plasma cell (PC) development is initiated following B cell activation and controlled by a B lymphocyte-induced maturation protein (Blimp)-1-dependent program involving the concerted action of several proplasma transcriptional regulators. However, the factors that control Blimp-1 expression remain largely unknown. In this context, mice deficient for all three of the Vav family of proteins (Vav^null) develop substantial B cell populations, including marginal zone B cells, yet have a virtual absence of serum Igs, indicating that Vav may be specifically required in PC development and Ig production. We show in this study that mature marginal zone B cells from Vav^null mice proliferate following stimulation with TLR ligands but exhibit severe defects in PC differentiation and Ig secretion. Under conditions inducing PC differentiation, Vav^null B cells fail to efficiently induce Blimp-1, X box-binding protein-1, J chain, or secretory Ig µ transcripts but express IFN-regulatory factor-4 at levels similar to wild-type cells. These data indicate a previously unknown role for Vav as an upstream regulator of Blimp-1.

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 National Institutes of Health Grants P30-AR048335, R01-AI061077 (to W.S.), and 5-T32-AI07163-27 (to L.M.S.).

² Address correspondence and reprint requests to Dr. Wojciech Swat, Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110. E-mail address: swat{at}wustl.edu

³ Abbreviations used in this paper: PC, plasma cell; Blimp, B lymphocyte-induced maturation protein; IRF, IFN-regulatory factor; MZ, marginal zone; XBP, X box-binding protein; MFI, mean fluorescence intensity; WT, wild type.

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