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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 
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 
RNA
expression and the transcriptional activity of the germline
promoter, while enhancing activity of the germline 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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