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

Nature volume 383, pages 542–547 (1996)Cite this article

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 vitro1–3. Subsequent cloning studies led to identification of the coactivator as a single poly-peptide, 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 activation1–5. 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 pro- liferative response to surface IgM crosslinking is impaired, and there is a severe deficiency in the production of secondary immunoglobulin isotypes including IgGl, 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.

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Authors and Affiliations

  1. Laboratory of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, 10021, USA

    Unkyu Kim, Sean Stevens, Yan Luo & Robert G. Roeder

  2. Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, 10021, USA

    Xiao-Feng Qin, Shiaoching Gong & Michel Nussenzweig

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  1. Unkyu Kim
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  5. Yan Luo
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  7. Robert G. Roeder
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Kim, U., Qin, XF., Gong, S. et al. The B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes. Nature 383, 542–547 (1996). https://doi.org/10.1038/383542a0

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