Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappa B and neural tube closure

Bcl10, a CARD-containing protein identified from the t(1;14)(p22;q32) break point in MALT lymphomas, has been shown to induce apoptosis and activate NF -kappaB in vitro. We show that one-third of bcl10(-/-) embryos developed ex encephaly, leading to embryonic lethality. Surprisingly, bcl10(-/-) cells r etained susceptibility to various apoptotic stimuli in vivo and in vitro. H owever, surviving bcl10(-/-) mice were severely immunodeficient and bcl10(- /-) lymphocytes are defective in antigen receptor or PMA/lonomycin-induced activation. Early tyrosine phosphorylation, MAPK and AP-1 activation, and C a2+ signaling were normal in mutant lymphocytes, but antigen receptor-induc ed NF-kappaB activation was absent. Thus, Bcl10 functions as a positive reg ulator of lymphocyte proliferation that specifically connects antigen recep tor signaling in B and T cells to NF-kappaB activation.