Vasilis Samelis

ALT "Regulation of BCR-mediated Ca2+ mobilization by MIZ1-TIMBIM4 safeguards IgG1+ GC B cell positive selection": * The transition from IgM to affinity-matured IgG antibodies is vital for effective humoral immunity. This is facilitated by germinal centers (GCs) through affinity maturation and preferential accumulation of IgG+ B cells over IgM+ B cells. * However, it is not known whether the positive selection of the different immunoglobulin isotypes within GCs varies in its dependency on specific transcriptional mechanisms. * We found that MIZ1 was specifically required for IgG1+ GC B cell survival during positive selection, whereas IgM+ GC B cells were largely independent. * Mechanistically, MIZ1 induced TMBIM4, an ancestral anti-apoptotic protein that regulated inositol trisphosphate receptor mediated Ca2+ mobilization downstream of IgG1. * The MIZ1-TMBIM4 axis prevented mitochondria dysfunction-induced IgG1+ GC cell death caused by excessive Ca2+ accumulation.