Key Points: PTFL is a monoclonal B-cell neoplasia with low genomic complexity and recurrent TNFRSF14 mutations/deletions. The genetic profiles of conventional t(14;18)− and t(14;18)+ FL are similar but distinct from PTFL.

The mer receptor tyrosine kinase mediates phagocytosis of apoptotic cells and modulates cytokine production; it is also required for prevention of systemic autoimmune disease. Using a mer‐specific antibody, we have confirmed the presence of mer on macrophages and now report its expression on NK cells, NKT cells, and dendritic cells (DC). We found that DC do not require mer for ingestion of apoptotic cells, as DC from mer‐deficient mice phagocytose apoptotic cells normally. Mer was observed in splenic sections on cells outside follicular areas, probably representing DC and macrophages. Mer apparentlyparticipates in NKT‐cell antigen‐induced signaling, as NKT cells from mer‐deficient mice evinced much lower cytokine production after in vivo α‐galactosylceramide stimulation; this defect was intrinsic to the mer‐deficient NKT cells. Taken together, these studies show mer expression on cells of the innate immune system. Mer, through its binding of lipid antigens, may not only mediate ingestion of apoptotic cells, but also signal events in NK cells, NKT cells, and DC.

Bim, the B cell lymphoma 2–interacting (Bcl2-interacting) mediator, maintains immunological tolerance by deleting autoreactive lymphocytes through apoptosis. We report here that Bim is also, paradoxically, required for the activation of autoreactive T cells. Deletion of Bim in hematopoietic cells rendered mice resistant to autoimmune encephalomyelitis and diabetes, and Bim-deficient T cells had diminished cytokine production. Upon T cell receptor activation, Bim-deficient T cells exhibited severe defects in both calcium release and dephosphorylation of nuclear factor of activated T cells (NFAT) but maintained normal levels of activation of NF-κB and MAPKs. The defective calcium signaling in Bim-deficient T cells was associated with a significant increase in the formation of an inhibitory complex containing Bcl2 and the inositol triphosphate receptor (IP₃R). Thus, in addition to mediating the death of autoreactive T cells, Bim also controlled T cell activation through the IP₃R/calcium/NFAT pathway. These results indicate that a single protein is used to control both the activation and apoptosis of autoreactive T cells and may explain why Bim-deficient mice do not reject their own organs despite lacking thymic negative selection.