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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.
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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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