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B-cell-specif ic coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation

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Abstract

THE B-lymphocyte-specific transcriptional factor called Oct binding factor (OBF)-1, OCA-B or Bob1 (refs 1–3) is thought to be involved in the transcription of immunoglobulin genes through recruitment to the highly conserved octamer site of immunoglobulin promoters, mediated by either Oct-1 or Oct-2. To define the in vivo role of OBF-1 we have used gene targeting in embryonic stem cells to generate mice lacking the coactivator OBF-1. Such OBF-1−/− mice are born normally, are fertile and seem healthy, and surprisingly, rearrangement and transcription of immunoglobulin genes are largely unaffected. However, mice deficient in OBF-1 have reduced numbers of mature B cells and a severe reduction in the number of recirculating B cells, but otherwise show normal B-cell differentiation. Serum IgA and particularly IgG levels are greatly reduced. If mutant mice are immunized with either a thymus-independent or a thymus-dependent antigen, their immune responses are dramatically weakened. Strikingly, germinal centres completely fail to develop after immunization with thymus-dependent antigen. Our results demonstrate that in vivo OBF-1 is not required for initial transcription of immunoglobulin genes or for B cell development, but instead is essential for the response of B cells to antigens, and is required for the formation of germinal centres.

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Author notes

  1. Antonius Rolink: Basel Institute for Immunology, Grenzacherstrasse 487, CH-4005 Basel, Switzerland

  2. Marie H. Kosco-Vilbois: Glaxo Institute for Molecular Biology, ch. des Aulx 14, CH-1228 Plan-les-Ouates, Switzerland

Authors and Affiliations

  1. Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4002, Basel, Switzerland

    Daniel B. Schubart, Antonius Rolink, Marie H. Kosco-Vilbois, Florence Botteri & Patrick Matthias

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  1. Daniel B. Schubart
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  2. Marie H. Kosco-Vilbois
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  3. Florence Botteri
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  4. Patrick Matthias
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Schubart, D., Rolink, A., Kosco-Vilbois, M. et al. B-cell-specif ic coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation. Nature 383, 538–542 (1996). https://doi.org/10.1038/383538a0

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  • DOI: https://doi.org/10.1038/383538a0

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