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. 2011 Nov 23;35(5):746-56.
doi: 10.1016/j.immuni.2011.10.011. Epub 2011 Nov 9.

Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase-mediated inhibitory signaling cascade required for B cell anergy

Shannon K O'Neill  1 , Andrew Getahun, Stephen B Gauld, Kevin T Merrell, Idan Tamir, Mia J Smith, Joseph M Dal Porto, Quan-Zhen Li, John C Cambier
Affiliations

Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase-mediated inhibitory signaling cascade required for B cell anergy

Shannon K O'Neill et al. Immunity. .

Abstract

Anergic B cells are characterized by impaired signaling and activation after aggregation of their antigen receptors (BCR). The molecular basis of this impairment is not understood. In studies reported here, Src homology-2 (SH2)-containing inositol 5-phosphatase SHIP-1 and its adaptor Dok-1 were found to be constitutively phosphorylated in anergic B cells, and activation of this inhibitory circuit was dependent on Src-family kinase activity and consequent to biased BCR immunoreceptor tyrosine-based activation motif (ITAM) monophosphorylation. B cell-targeted deletion of SHIP-1 caused severe lupus-like disease. Moreover, absence of SHIP-1 in B cells led to loss of anergy as indicated by restoration of BCR signaling, loss of anergic surface phenotype, and production of autoantibodies. Thus, chronic BCR signals maintain anergy in part via ITAM monophosphorylation-directed activation of an inhibitory signaling circuit involving SHIP-1 and Dok-1.

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Conflict of interest statement

The authors have no conflicting financial interests.

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References

    1. Adachi T, Wienands J, Tsubata T, Kurosaki T. Interdomain A is crucial for ITAM-dependent and -independent regulation of Syk. Biochem Biophys Res Commun. 2007;364:111–117. - PubMed
    1. Auborn KJ, Qi M, Yan XJ, Teichberg S, Chen D, Madaio MP, Chiorazzi N. Lifespan is prolonged in autoimmune-prone (NZB/NZW) F1 mice fed a diet supplemented with indole-3-carbinol. J Nutr. 2003;133:3610–3613. - PubMed
    1. Benschop RJ, Aviszus K, Zhang X, Manser T, Cambier JC, Wysocki LJ. Activation and anergy in bone marrow B cells of a novel immunoglobulin transgenic mouse that is both hapten specific and autoreactive. Immunity. 2001;14:33–43. - PubMed
    1. Blasioli J, Goodnow CC. Lyn/CD22/SHP-1 and their importance in autoimmunity. Curr Dir Autoimmun. 2002;5:151–160. - PubMed
    1. Blery M, Tze L, Miosge LA, Jun JE, Goodnow CC. Essential role of membrane cholesterol in accelerated BCR internalization and uncoupling from NF-kappa B in B cell clonal anergy. J Exp Med. 2006;203:1773–1783. - PMC - PubMed

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