OCA-B INTEGRATES B-CELL ANTIGEN RECEPTOR-MEDIATED, CD40L-MEDIATED ANDIL-4-MEDIATED SIGNALS FOR THE GERMINAL CENTER PATHWAY OF B-CELL DEVELOPMENT

Many of the key decisions in lymphocyte differentiation and activation are dependent on integration of antigen receptor and co-receptor sign als. Although there is significant understanding of these receptors an d their signaling pathways, little is known about the molecular requir ements for signal integration at the level of activation of gene expre ssion. Here we show that in primary B cells, expression of the B-cell specific transcription coactivator OCA-B (also known as OBF-1 or Bob-1 ) is regulated synergistically by the B-cell antigen receptor, CD40L a nd interleukin signaling pathways. Consistent with the requirement for multiple T cell-dependent signals to induce OCA-B, we find that OCA-B protein is highly expressed in germinal center B cells. Accordingly, germinal center formation is blocked completely in the absence of OCA- B expression in B cells, whereas the helper functions of OCA-B-deficie nt T cells are indistinguishable from controls, The requirement for OC A-B expression in B cells is germinal center specific since the develo pment of primary B cell follicles, the marginal zone and plasma cells are all intact. Thus, OCA-B is the first example of a transcriptional coactivator that is both synergistically induced by and required for i ntegration of signals that mediate cell fate decisions.