Title: BOB.1/OBF.1 - A Critical Regulator of B Cell Function
Volume: 2
Issue: 1
Author(s): Cornelia Brunner and Thomas Wirth
Affiliation:
Keywords:
BOB.1/OBF.1, OCA-B, germinal center, target genes, B cell development, B cell function, octamer motif
Abstract: The transcriptional coactivator BOB.1/OBF.1 binds as a ternary complex with the transcription factors Oct-1 and Oct-2 to DNA and induces octamer-dependent transcription. BOB.1/OBF.1 was shown to be necessary at multiple stages of B cell development, in the bone marrow as well as at late stages in secondary lymphoid organs. Bone marrow B cells from BOB.1/OBF.1-deficient mice show increased apoptosis accompanied with decreased expression levels of the anti-apoptotic protein Bcl2. Although transgenic B cell-specific expression of Bcl2 rescued the numbers and maturation of BOB.1/OBF.1-deficient B cells in the bone marrow as well as in peripheral lymphoid organs, the B cell function was still severely impaired. The most prominent characteristic of BOB.1/OBF.1 knock-out mice is the complete failure to form germinal centers upon immunization with thymic-dependent antigens and consequently a massive defect in production of secondary Ig isotypes. In addition, the marginal zone B cell compartment, first line defence against blood born antigens, is virtually absent in BOB.1/OBF.1 -/- animals. A large number of genes specifically expressed in B cells contain octamer motifs in their regulatory regions, but only a small number of BOB.1/OBF.1 dependent genes are described yet. To understand the molecular basis of BOB.1/OBF.1 function in B cell development we and others searched for BOB.1/OBF.1 target genes. A large number of BOB.1/OBF.1-dependent genes were identified, which are involved in different aspects of lymphocyte development and signaling, supporting the critical regulatory role of BOB.1/OBF.1 for lymphocyte function. Here we summarize recent developments highlighting the central role that BOB.1/OBF.1 plays in B lymphocytes.
