SIRPα on Mouse B1 Cells Restricts Lymphoid Tissue Migration and Natural Antibody Production

The inhibitory immunoreceptor SIRP alpha is expressed on myeloid and neuronal cells and interacts with the broadly expressed CD47. CD47-SIRP alpha interactions form an innate immune checkpoint and its targeting has shown promising results in cancer patients. Here, we report expression of SIRP alpha on B1 lymphocytes, a subpopulation of murine B cells responsible for the production of natural antibodies. Mice defective in SIRP alpha signaling (SIRP alpha(Delta CYT)mice) displayed an enhanced CD11b/CD18 integrin-dependent B1 cell migration from the peritoneal cavity to the spleen, local B1 cell accumulation, and enhanced circulating natural antibody levels, which was further amplified upon immunization with T-independent type 2 antigen. As natural antibodies are atheroprotective, we investigated the involvement of SIRP alpha signaling in atherosclerosis development. Bone marrow (SIRP alpha(Delta CYT)>LDLR-/-) chimaeric mice developed reduced atherosclerosis accompanied by increased natural antibody production. Collectively, our data identify SIRP alpha as a unique B1 cell inhibitory receptor acting to control B1 cell migration, and imply SIRP alpha as a potential therapeutic target in atherosclerosis.