AUTHOR=Franke Katka , Pillai Saravanan Y. , Hoogenboezem Mark , Gijbels Marion J. J. , Matlung Hanke L. , Geissler Judy , Olsman Hugo , Pottgens Chantal , van Gorp Patrick J. , Ozsvar-Kozma Maria , Saito Yasuyuki , Matozaki Takashi , Kuijpers Taco W. , Hendriks Rudi W. , Kraal Georg , Binder Christoph J. , de Winther Menno P. J. , van den Berg Timo K. TITLE=SIRPα on Mouse B1 Cells Restricts Lymphoid Tissue Migration and Natural Antibody Production JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.570963 DOI=10.3389/fimmu.2020.570963 ISSN=1664-3224 ABSTRACT=

The inhibitory immunoreceptor SIRPα is expressed on myeloid and neuronal cells and interacts with the broadly expressed CD47. CD47-SIRPα interactions form an innate immune checkpoint and its targeting has shown promising results in cancer patients. Here, we report expression of SIRPα on B1 lymphocytes, a subpopulation of murine B cells responsible for the production of natural antibodies. Mice defective in SIRPα signaling (SIRPαΔCYT 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 SIRPα signaling in atherosclerosis development. Bone marrow (SIRPαΔCYT>LDLR−/−) chimaeric mice developed reduced atherosclerosis accompanied by increased natural antibody production. Collectively, our data identify SIRPα as a unique B1 cell inhibitory receptor acting to control B1 cell migration, and imply SIRPα as a potential therapeutic target in atherosclerosis.