The B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes.

TitleThe B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes.
Publication TypeJournal Article
Year of Publication1996
AuthorsKim U, Qin XF, Gong S, Stevens S, Luo Y, Nussenzweig M, Roeder RG
JournalNature
Volume383
Issue6600
Pagination542-7
Date Published1996 Oct 10
ISSN0028-0836
KeywordsAnimals, 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
Abstract

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.

DOI10.1038/383542a0
Alternate JournalNature
PubMed ID8849728