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The Journal of Immunology, 1998, 161: 2906-2918.
Copyright © 1998 by The American Association of Immunologists

Overexpression of BSAP/Pax-5 Inhibits Switching to IgA and Enhances Switching to IgE in the I.29µ B Cell Line1

Gang Qiu and Janet Stavnezer2

Department of Molecular Genetics and Microbiology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655

B cell-specific activator protein (BSAP)/Pax-5 is a paired domain DNA-binding protein expressed in the developing nervous system, testis, and in all B lineage cells, except terminally differentiated plasma cells. BSAP regulates transcription of several genes expressed in B cells and also the activity of the 3' IgH enhancer. As it has binding sites within or 5' to the switch regions of nearly all Ig heavy chain C region genes and also is known to increase transcription of the germline {epsilon} RNA, BSAP has been hypothesized to be involved in regulation of Ab class switch recombination. To directly examine the effects of BSAP on isotype switching, we use a tetracycline-regulated expression system to overexpress BSAP in the surface IgM+ I.29µ B cell line, a mouse cell line that can be induced to undergo class switch recombination. We find that overexpression of BSAP inhibits switching to IgA in I.29µ cells stimulated with LPS + TGF-ß1 + nicotinamide, but enhances switching to IgE in cells stimulated with LPS + IL-4 + nicotinamide. Parallel to its effects on switching, overexpression of BSAP inhibits germline {alpha} RNA expression and the transcriptional activity of the germline {alpha} promoter, while enhancing activity of the germline {epsilon} promoter. Proliferation of I.29µ cells is not affected in this system. The possible mechanisms and significance of the effect of BSAP on isotype switching are discussed.




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