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Distinct Roles for Bruton's Tyrosine Kinase in B Cell Immune Synapse Formation.

Sara Roman-Garcia | Sara V Merino-Cortes | Sofia R Gardeta | Marjolein J W de Bruijn | Rudi W Hendriks | Yolanda R Carrasco
Frontiers in immunology | 2018

Bruton's tyrosine kinase (Btk) has a key role in the signaling pathways of receptors essential for the B lymphocyte response. Given its implication in B cell-related immunodeficiencies, leukemias/lymphomas and autoimmunity, Btk is studied intensely and is a target for therapy. Here, using primary B cells from distinct mouse models and the pharmacological inhibitors ibrutinib and acalabrutinib, we report distinct roles for Btk in antigen-triggered immune synapse (IS) formation. Btk recruitment to the plasma membrane regulates the B cell ability to trigger IS formation as well as its appropriate molecular assembly; Btk shuttling/scaffold activities seem more relevant than the kinase function on that. Btk-kinase activity controls antigen accumulation at the IS through the PLCγ2/Ca2+ axis. Impaired Btk membrane-recruitment or kinase function likewise alters antigen-triggered microtubule-organizing center (MTOC) polarization to the IS, B cell activation and proliferation. Data also show that, for B cell function, IS architecture is as important as the quantity of antigen that accumulates at the synapse.

Pubmed ID: 30237801

Associated grants

  • Agency: Worldwide Cancer Research, United Kingdom
    Id: 15-1322

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