Abstract
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.
Original language | English |
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Article number | 570963 |
Number of pages | 13 |
Journal | Frontiers in Immunology |
Volume | 11 |
DOIs | |
Publication status | Published - 9 Oct 2020 |
Keywords
- B1 cells
- natural antibodies
- atherosclerosis
- immune checkpoint
- inhibitory receptor
- SIRP alpha
- CD47
- CD11b
- CD18-integrin
- OXIDATION-SPECIFIC EPITOPES
- SIGNAL-REGULATORY PROTEIN
- B-1 CELLS
- PROMOTES ATHEROSCLEROSIS
- NEGATIVE REGULATION
- DENDRITIC CELLS
- OXIDIZED LDL
- SIGLEC-G
- RECEPTOR
- AUTOANTIBODIES