Role of OCA-B in 3 '-IgH enhancer function

OCA-B (alternately called Bob1 and OBF-1) is a B cell-specific coactivator that interacts with the ubiquitously expressed Oct-1 and the B cell-restric ted Oct-2 to activate transcription via the octamer site (5'-ATGCAAAT-3'), OCA-B-/- mice appear to undergo normal Ag-independent B cell maturation. Ho wever, Ag-dependent B cell differentiation, including germinal center forma tion, production of secondary Ig isotypes, and proliferation in response to surface Ig cross-linking, is greatly affected. We demonstrate that the obs erved reductions in expression of class-switched isotypes in OCA-B-/- mice may be due in part to deficiencies in the function of the 3'-IgH enhancer e lements. Furthermore, we find that surface Ig cross-linking represses all t he Ig enhancers and that this repression is absent in OCA-B-/- B cells. The se results suggest an important role for OCA-B in Ig enhancer function in v ivo.