Regulation of B cell development and lymphocyte function by transcriptional coactivator OCA-B.

OCA-B (OCT Coactivator from B cells) is highly expressed in B cells and is the first-identified tissue-specific transcriptional coactivator. Mechanistically, OCA-B is recruited to target genes through primary interactions with DNA-binding transcription factors OCT1/OCT2, as well as secondary interactions with MEF2B, and its effector functions in activating transcription involve interactions with the Mediator coactivator complex. Physiologically, OCA-B plays an essential role in antigen-stimulated Germinal Center (GC) formation and transcription of secondary immunoglobulin (Ig) genes. OCA-B also regulates bone marrow and peripheral B cell development. While GC B cell-specific inactivation of Oca-B is sufficient to cause GC defects, OCA-B function in follicular T helper (Tfh) cells also plays an important role in GC reactions. In GC B cells, OCA-B-dependent genes include known GC regulatory genes such as Bcl6, Mef2b and Irf4. In CD4+ memory T cells, OCA-B is required to maintain a subset of genes, including Il2, in a transcriptionally poised state, enabling their rapid and robust up-regulation upon repeated stimulation. Moreover, recent studies have indicated an essential role for OCA-B in B-cell malignancy and multiple autoimmune diseases, highlighting OCA-B as a potential therapeutic target for these diseases.