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The Journal of Immunology, 2007, 179, 1516-1523
Copyright © 2007 by The American Association of Immunologists, Inc.

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CD86 Regulates IgG1 Production via a CD19-Dependent Mechanism1

Nicholas W. Kin2 and Virginia M. Sanders3

Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210

CD86 signals directly in a B cell to activate PI3K and increase the rate of IgG1 production, without affecting germline transcription. However, the mechanism by which CD86 activates PI3K in a B cell and the relevance of CD86 stimulation in vivo remains unknown. We show that the addition of CD28/Ig to CD40 ligand/IL-4-activated wild-type, but not CD86- or CD19-deficient, B cells increased the level of phosphorylation for Lyn and CD19, as well as the amount of Lyn, Vav, and PI3K that immunoprecipitated with CD19. Adoptive transfer of CD86-deficient B cells and wild-type CD4+ T cells into RAG2-deficient mice and immunization with trinitrophenylated keyhole limpet hemocyanin resulted in an IL-4 and germline IgG1 response equivalent to control mice, but a decrease in serum IgG1. Thus, our findings suggest that CD86 plays a key role in regulating the level of IgG1 produced in vitro and in vivo, and that Lyn and CD19 may be the signaling intermediates activated by CD86 proximal to PI3K.

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 research funds from the National Institutes of Health Grant AI37326. N.W.K. is a recipient of a training grant award from National Institutes of Health Grant T32 AI55411.

2 This research is part of the dissertation research conducted by Nicholas W. Kin who is a predoctoral student in the Integrated Biomedical Science Graduate Program, The Ohio State University, Columbus, OH 43210.

3 Address correspondence and reprint requests to Dr. Virginia M. Sanders, 2194 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210. E-mail address: Sanders.302{at}osu.edu

4 Abbreviations used in this paper: DC, dendritic cells; WT, wild type; PTK, protein tyrosine kinase; KLH, keyhole limpet hemocyanin; CD40L, CD40 ligand.




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