|Title||The B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes.|
|Publication Type||Journal Article|
|Year of Publication||1996|
|Authors||Kim U, Qin XF, Gong S, Stevens S, Luo Y, Nussenzweig M, Roeder RG|
|Date Published||1996 Oct 10|
|Keywords||Animals, B-Lymphocytes, Cell Differentiation, Flow Cytometry, Gene Targeting, Genes, Immunoglobulin, Germinal Center, Immunoglobulin Class Switching, Immunoglobulin Isotypes, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mutagenesis, Trans-Activators|
OCA-B was initially identified as a B-cell-restricted coactivator that functions with octamer binding transcription factors (Oct-1 and Oct-2) to mediate efficient cell type-specific transcription of immunoglobulin promoters in vitro. Subsequent cloning studies led to identification of the coactivator as a single polypeptide, designated either as OCA-B (ref. 3), OBF-1 (ref. 4) or Bob-1 (ref. 5). OCA-B itself does not bind to DNA directly, but interacts with either Oct-1 or Oct-2 to potentiate transcriptional activation. To determine the biological role of OCA-B, we generated OCA-B-deficient mice by gene targeting. Mice lacking OCA-B undergo normal antigen-independent, B-cell differentiation, including appropriate expression of both immunoglobulin genes and other early B-cell-restricted genes. However, antigen-dependent maturation of B cells is greatly affected. The proliferative response to surface IgM crosslinking is impaired, and there is a severe deficiency in the production of secondary immunoglobulin isotypes including IgG1, IgG2a, IgG2b, IgG3, IgA and IgE in OCA-B-deficient B cells. This defect is not due to a failure of the isotype switching process, but rather to reduced levels of transcription from normally switched immunoglobulin heavy-chain loci. In accord with the defective isotype production, germinal centre formation is absent in these mutant mice.