The B lymphocyte-specific coactivator BOB.1/OBF.1 is required at multiple stages of B-cell development

The transcriptional coactivator BOB.1/OBF.1 confers B-cell specificity on t he transcription factors Oct1 and Oct2 at octamer site-containing promoters . A hallmark of the BOB.1/OBF.1 mutation in the mouse is the absence of ger minal center development in secondary lymphoid organs, demonstrating the re quirement for BOB.1/OBF.1 in antigen-dependent stages of B-cell differentia tion. Here we analyzed earlier stages of B lymphopoiesis in BOB.1/OBF.1-def icient mice. Examination of B-cell development in the bone marrow revealed that the numbers of transitional immature (B220(+) IgM(hi)) B cells were re duced and that B-cell apoptosis was increased. When in competition with wil d-type cells, BOB.1/OBF.1(-/-) bone marrow cells exhibited defects in repop ulating the bone marrow B-cell compartment and were unable to establish a p resence in the periphery of host mice. The defective bone marrow population s in BOB.1/OBF.1(-/-) mice were rescued by conditional expression of a BOB. 1/OBF.1 transgene controlled by the tetracycline gene expression system. Ho wever, the restored populations did not restore the numbers of IgD(hi) B ce lls in the periphery, where the BOB.1/OBF.1 transgene was not expressed. Th ese results show that BOB.1/OBF.1(-/-) B cells exhibit multistage defects i n B-cell development, including impaired production of transitional B cells and defective maturation of recirculating B cells.