BOB.1/OBF.1 is required during B cell ontogeny for B cell differentiation and germinal center function

BOB.1/OBF.1 is a lymphocyte-specific transcriptional co-activator of octamer-dependent transcription. It regulates the expression of genes important for lymphocyte physiology together with the Oct-1 and Oct-2 transcription factors. So far, BOB.1/OBF.1 has been studied in conventional knockout mice, whereby a function of BOB.1/OBF.1 in B but also in T cells was described. The main characteristic of BOB.1/OBF.1-deficient mice is the complete absence of germinal centers. However, it is entirely unsolved at which stage of B cell development BOB.1/OBF.1 expression is essential for germinal center formation. Still, it is not known whether defects observed late in B cell development of BOB.1/OBF.1-deficient mice are merely a consequence of defective early B cell development. To answer the question, whether BOB.1/OBF.1 expression is required before or during the process of germinal center formation, we established a mouse system, which allows the conditional deletion of BOB.1/OBF.1 at different stages of B cell development. Our data reveal a requirement for BOB.1/OBF.1 during both early antigen-independent and late antigen-dependent B cell development, and further a requirement for efficient germinal center reaction during complete B cell ontogeny. By specifically deleting BOB.1/OBF.1 in germinal center B cells, we provide evidence that the failure to form germinal centers is a germinal center B cell intrinsic defect and not exclusively a consequence of defective early B cell maturation.

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