The transcription factor BSAP (NF-HB) is essential for immunoglobulin germ-line ε transcription

Treatment of murine splenic B lymphocytes and certain B-lineage cell lines with mitogen (LPS) and the lymphokine IL-4 has been shown to induce expression of germ-line ε transcripts (lε transcripts) and class switching to the Cε gene. Three protein complexes, one of which (complex 3) is constitutively expressed, have been shown to bind to a 179-base pair LPS/IL- 4-responsive lε promoter (Rothman, P., S. C. Li, B. Gorham, L. Glimcher, F. W. Alt, and M. Boothby, 1991. Mol. Cell. Biol. 11:5551). Complex 3 is indispensable for this inducible promoter activity. In this report, we have used electrophoretic mobility shift assays (EMSA) to demonstrate that the early B cell-specific transcription factor (BSAP) is involved in the formation of complex 3. In addition, BSAP is implicated functionally in lε transcription because a BSAP binding site either from a sea urchin histone promoter (H2A-2.2) or from 5' of murine immunoglobulin Sγ2a can substitute for the ε-associated site (ε(foot), as assayed by transient transfection assays of the lε:CAT reporter constructs into the M12.4.1 B cell line. Like the sea urchin histone BSAP site, the complex 3 binding site (ε(foot)) functions as an upstream promoter element when assayed in the OVEC vector. These results indicate that BSAP is an essential protein required for LPS/IL- 4 induction of the lε promoter. In addition, experiments showing that a BSAP binding site from 5' of Sγ2a also functions as an upstream promoter element in OVEC suggest a potential role for BSAP in regulation of the IgG2a isotype.