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

Nat Commun. 2013;4:2813. doi: 10.1038/ncomms3813.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis*
  • Autoantibodies / metabolism
  • B-Lymphocyte Subsets / immunology*
  • CD11b Antigen / metabolism*
  • Cell Proliferation
  • Cell Survival / immunology
  • Female
  • Immune Tolerance*
  • Lupus Erythematosus, Systemic / etiology*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation, Missense
  • Receptors, Antigen, B-Cell / physiology*
  • Up-Regulation / immunology


  • Autoantibodies
  • CD11b Antigen
  • Receptors, Antigen, B-Cell