B-CELL-SPECIFIC COACTIVATOR OBF-1 OCA-B/BOB1 REQUIRED FOR IMMUNE-RESPONSE AND GERMINAL CENTER FORMATION/

THE B-lymphocyte-specific transcriptional factor called Oct binding fa ctor (OBF)-1, OCA-B or Bob1 (refs 13) is thought to be involved in the transcription of immunoglobulin genes through recruitment to the high ly conserved octamer site of immunoglobulin promoters, mediated by eit her Oct-1 or Oct-2. To define the in vivo role of OBP-1 we have used g ene targeting in embryonic stem cells to generate mice lacking the coa ctivator OBP-1. Such OBF-1(-/-) mice are born normally, are fertile an d seem healthy, and surprisingly, rearrangement and transcription of i mmunoglobulin genes are largely unaffected. However, mice deficient in OBF-1 have reduced numbers of mature B cells and a severe reduction i n the number of recirculating B cells, but otherwise show normal B-cel l differentiation. Serum IgA and particularly IgG levels are greatly r educed. If mutant mice are immunized with either a thymus-independent or a thymus-dependent antigen, their immune responses are dramatically weakened. Strikingly, germinal centres completely fail to develop aft er immunization with thymus-dependent antigen. Our results demonstrate that in vivo OBF-1 is not required for initial transcription of immun oglobulin genes or for B cell development, but instead is essential fo r the response of B cells to antigens, and is required for the formati on of germinal centres.