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Contribution of BCAP to maintenance of mature B cells through c-Rel

Nature Immunology volume 4, pages 780–786 (2003)Cite this article

Abstract

Mice deficient in the B cell adaptor for phosphoinositide 3-kinase (BCAP) have reduced numbers of mature B lymphocytes, which show defects in cell survival and proliferation. We found here that the NF-κB (Rel) pathway was impaired in BCAP-deficient mature B cells and that NF-κB target genes, indispensable for cell survival and division, were not induced in response to B cell receptor (BCR) stimulation. Among the NF-κB (Rel) family, expression of c-Rel was specifically reduced in BCAP-deficient B cells. Retrovirus-mediated reintroduction of c-Rel restored the pool size of immunoglobulin (Ig)MloIgDhi mature B cells in the spleen as well as proliferative responses to BCR stimulation. These results indicate BCAP is essential in the maintenance of mature B cells through functional coupling with c-Rel.

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Figure 1: Defects of BCAP-deficient mature B cells in both cell survival and division.
Figure 2: Attenuated expression of key components for cell survival and division in BCAP-deficient mature B cells.
Figure 3: Altered NF-κB DNA-binding activity and selective reduction of c-Rel in BCAP-deficient B cells.
Figure 4: Restoration of the mature B cell subpopulation by reconstitution with BCAP-deficient bone marrow cells expressing exogenous c-Rel.
Figure 5: Restoration of growth response of BCAP-deficient mature B cells by reconstitution with c-Rel.

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Acknowledgements

We thank Y. Shima and K. Sumi for technical assistance, and M. Matsumoto for suggestions. Supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to T.Y. and T.K.), The Mochida Memorial Foundation for Medical and Pharmaceutical Research (to T.Y.) and NOVARTIS Foundation (Japan) for the Promotion of Science (to T.Y.).

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Authors and Affiliations

  1. Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, 570-8506, Japan

    Tetsuo Yamazaki & Tomohiro Kurosaki

  2. Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, 10-15 Fumizono-cho, Moriguchi, 570-8506, Japan

    Tomohiro Kurosaki

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  1. Tetsuo Yamazaki
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  2. Tomohiro Kurosaki
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Correspondence to Tomohiro Kurosaki.

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Yamazaki, T., Kurosaki, T. Contribution of BCAP to maintenance of mature B cells through c-Rel. Nat Immunol 4, 780–786 (2003). https://doi.org/10.1038/ni949

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