APRIL mediates peritoneal B-1 cell homeostasis.

BLyS (B lymphocyte stimulator) family cytokines and receptors play key roles in B-2 cell maturation and survival, but their importance for B-1 cells remains less clear. Here we use knockout mice to show that APRIL (A proliferation-inducing ligand), but not BLyS, plays a role in peritoneal B-1 cell maintenance. APRIL likely exerts its effects on peritoneal B-1 cells through binding to HSPG (heparan sulfate proteoglycans) rather than to the TACI (transmembrane activator and cyclophilin ligand interactor) receptor. Finally, we show that peritoneal macrophages express high levels of APRIL message, and are a likely local source of the cytokine in this anatomic locale.