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Integrin CD11b negatively regulates BCR signalling to maintain autoreactive B cell tolerance

Author

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  • Chuanlin Ding

    (Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine
    University of Louisville School of Medicine)

  • Yunfeng Ma

    (Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine)

  • Xingguo Chen

    (Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine
    Nanjing First Hospital Affiliated to Nanjing Medical University)

  • Min Liu

    (Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine)

  • Yihua Cai

    (Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine)

  • Xiaoling Hu

    (Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine)

  • Dong Xiang

    (Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine
    University of Louisville School of Medicine)

  • Swapan Nath

    (Arthritis and Clinical Immunology Group, Oklahoma Medical Research Foundation)

  • Huang-ge Zhang

    (University of Louisville School of Medicine
    Louisville Veterans Administration Medical Center)

  • Hong Ye

    (Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine)

  • David Powell

    (University of Louisville School of Medicine)

  • Jun Yan

    (Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville School of Medicine
    University of Louisville School of Medicine
    University of Louisville School of Medicine)

Abstract

A variant of the integrin-α-M (CD11b) gene has been linked to the pathogenesis of systemic lupus erythematosus. However, how this genotype results in the lupus phenotype is not fully understood. Here we show that autoreactive B cells lacking CD11b exhibit a hyperproliferative response to B cell receptor (BCR) crosslinking and enhanced survival. In vivo engagement of BCR in CD11b-deficient mice leads to increased autoAb production and kidney Ig deposition. In addition, CD11b-deficient autoreactive B cells have decreased tyrosine phosphorylation including Lyn and CD22 with decreased phosphatase SHP-1 recruitment but increased calcium influx. Results obtained using B cells transfected with the wild type or rs1143679 lupus-associated variant of CD11b suggest that this mutation completely abrogates the regulatory effect of CD11b on BCR signalling. This is through disruption of CD22–CD11b direct binding. These results reveal a previously unrecognized role of CD11b in maintaining autoreactive B cell tolerance.

Suggested Citation

  • Chuanlin Ding & Yunfeng Ma & Xingguo Chen & Min Liu & Yihua Cai & Xiaoling Hu & Dong Xiang & Swapan Nath & Huang-ge Zhang & Hong Ye & David Powell & Jun Yan, 2013. "Integrin CD11b negatively regulates BCR signalling to maintain autoreactive B cell tolerance," Nature Communications, Nature, vol. 4(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3813
    DOI: 10.1038/ncomms3813
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