Bcl10 Is a Positive Regulator of Antigen Receptor–Induced Activation of NF-κ B and Neural Tube Closure

Bcl10, a CARD-containing protein identified from the t(1;14)(p22;q32) breakpoint in MALT lymphomas, has been shown to induce apoptosis and activate NF- κ B in vitro. We show that one-third of bcl10 −/− embryos developed exencephaly, leading to embryonic lethality. Surprisingly, bcl10 −/− cells retained susceptibility to various apoptotic stimuli in vivo and in vitro. However, surviving bcl10 −/− mice were severely immunodeficient and bcl10 −/− lymphocytes are defective in antigen receptor or PMA/Ionomycin-induced activation. Early tyrosine phosphorylation, MAPK and AP-1 activation, and Ca 2+ signaling were normal in mutant lymphocytes, but antigen receptor–induced NF- κ B activation was absent. Thus, Bcl10 functions as a positive regulator of lymphocyte proliferation that specifically connects antigen receptor signaling in B and T cells to NF- κ B activation.