Frontiers in Immunology (Oct 2020)

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

  • Katka Franke,
  • Saravanan Y. Pillai,
  • Mark Hoogenboezem,
  • Marion J. J. Gijbels,
  • 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,
  • Taco W. Kuijpers,
  • Rudi W. Hendriks,
  • Georg Kraal,
  • Christoph J. Binder,
  • Menno P. J. de Winther,
  • Menno P. J. de Winther,
  • Timo K. van den Berg,
  • Timo K. van den Berg

DOI
https://doi.org/10.3389/fimmu.2020.570963
Journal volume & issue
Vol. 11

Abstract

Read online

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.

Keywords