Overexpression of BSAP/Pax-5 inhibits switching to IgA and enhances switching to IgE in the I.29 mu B cell line.
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.29 mu 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.29 mu cells stimulated with LPS + TGF-beta 1 + 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.29 mu cells is not affected in this system. The possible mechanisms and significance of the effect of BSAP on isotype switching are discussed.
Qiu
G
G
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655-0122, USA.
Stavnezer
J
J
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000235:genetics; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007137:Immunoglobulin alpha-Chains / Q000235:genetics; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics; D007148:Immunoglobulin mu-Chains; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016393:Lymphoma, B-Cell; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051757:PAX5 Transcription Factor; D011401:Promoter Regions, Genetic / Q000276:immunology; D013752:Tetracycline / Q000494:pharmacology; D014157:Transcription Factors; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D007070:Immunoglobulin A; D007137:Immunoglobulin alpha-Chains; D007139:Immunoglobulin epsilon-Chains; D007148:Immunoglobulin mu-Chains; D007166:Immunosuppressive Agents; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D014157:Transcription Factors; D007073:Immunoglobulin E; D013752:Tetracycline