Regulation of NF-κB-Dependent Lymphocyte Activation and Development by Paracaspase

Abstract

Paracaspase (MALT1), a member of an evolutionarily conserved superfamily of caspase-like proteins, has been shown to bind and colocalize with the protein Bcl10 in vitro and, because of this association, has been suggested to be involved in the CARMA1-Bcl10 pathway of antigen-induced nuclear factor κB (NF-κB) activation. We demonstrate that primary T and B lymphocytes from paracaspase-deficient mice are defective in antigen-receptor–induced NF-κB activation, cytokine production, and proliferation. Paracaspase acts downstream of Bcl10 to induce NF-κB activation and is required for the normal development of B cells, indicating that paracaspase provides the missing link between Bcl10 and activation of the IκB kinase complex.