Role of OCA-B in 3′-IgH Enhancer Function

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Abstract
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-restricted Oct-2 to activate transcription via the octamer site (5′-ATGCAAAT-3′). OCA-B−/− mice appear to undergo normal Ag-independent B cell maturation. However, Ag-dependent B cell differentiation, including germinal center formation, production of secondary Ig isotypes, and proliferation in response to surface Ig cross-linking, is greatly affected. We demonstrate that the observed 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 elements. Furthermore, we find that surface Ig cross-linking represses all the Ig enhancers and that this repression is absent in OCA-B−/− B cells. These results suggest an important role for OCA-B in Ig enhancer function in vivo.