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

Autor: Katka Franke, Saravanan Y. Pillai, Mark Hoogenboezem, Marion J. J. Gijbels, Hanke L. Matlung, Judy Geissler, Hugo Olsman, Chantal Pottgens, Patrick J. van Gorp, Maria Ozsvar-Kozma, Yasuyuki Saito, Takashi Matozaki, Taco W. Kuijpers, Rudi W. Hendriks, Georg Kraal, Christoph J. Binder, Menno P. J. de Winther, Timo K. van den Berg
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Frontiers in Immunology, Vol 11 (2020)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2020.570963
Popis: 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.
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