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 PLCĪ³2/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.

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Frontiers in Immunology
Department of Pulmonology

Roman-Garcia, S. (Sara), Merino-Cortes, S.V. (Sara V.), Gardeta, S.R. (Sofia R.), de Bruijn, M., Hendriks, R., & Carrasco, Y.R. (Yolanda R.). (2018). Distinct roles for Bruton's Tyrosine Kinase in B cell immune synapse formation. Frontiers in Immunology, 9(SEP). doi:10.3389/fimmu.2018.02027