TY - JOUR
T1 - SIRPα on Mouse B1 Cells Restricts Lymphoid Tissue Migration and Natural Antibody Production
AU - Franke, Katka
AU - Pillai, Saravanan Y.
AU - Hoogenboezem, Mark
AU - Gijbels, Marion J. J.
AU - Matlung, Hanke L.
AU - Geissler, Judy
AU - Olsman, Hugo
AU - Pottgens, Chantal
AU - van Gorp, Patrick J.
AU - Ozsvar-Kozma, Maria
AU - Saito, Yasuyuki
AU - Matozaki, Takashi
AU - Kuijpers, Taco W.
AU - Hendriks, Rudi W.
AU - Kraal, Georg
AU - Binder, Christoph J.
AU - de Winther, Menno P. J.
AU - van den Berg, Timo K.
PY - 2020/10/9
Y1 - 2020/10/9
N2 - 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.
AB - 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.
KW - B1 cells
KW - CD11b/CD18-integrin
KW - CD47
KW - SIRPα
KW - atherosclerosis
KW - immune checkpoint
KW - inhibitory receptor
KW - natural antibodies
UR - http://www.scopus.com/inward/record.url?scp=85094144392&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2020.570963
DO - https://doi.org/10.3389/fimmu.2020.570963
M3 - Article
C2 - 33162986
SN - 1664-3224
VL - 11
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 570963
ER -