| First Author | Roman-Garcia S | Year | 2018 |
| Journal | Front Immunol | Volume | 9 |
| Pages | 2027 | PubMed ID | 30237801 |
| Mgi Jnum | J:315931 | Mgi Id | MGI:6829428 |
| Doi | 10.3389/fimmu.2018.02027 | Citation | Roman-Garcia S, et al. (2018) Distinct Roles for Bruton's Tyrosine Kinase in B Cell Immune Synapse Formation. Front Immunol 9:2027 |
| abstractText | 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 PLCgamma2/Ca(2+) 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. |
