IL-33 activates B1 cells and exacerbates contact sensitivity.
B1 B cells produce natural IgM and play a critical role in the early defense against bacterial and viral infection. The polyreactive IgM also contributes to the clearance of apoptotic products and plays an important role in autoimmune pathogenesis. However, the mechanism of activation and proliferation of B1 cells remains obscure. In this study, we report that IL-33, a new member of IL-1 family, activates B1 cells, which express the IL-33 receptor α, ST2. IL-33 markedly activated B1 cell proliferation and enhanced IgM, IL-5, and IL-13 production in vitro and in vivo in a ST2-dependent manner. The IL-33-activated B1 cell functions could be largely abolished by IL-5 neutralization and partially reduced by T cell or mast cell deficiency in vivo. ST2-deficient mice developed less severe oxazolone-induced contact sensitivity (CS) than did wild-type (WT) mice. Furthermore, IL-33 treatment significantly exacerbated CS in WT mice with enhanced B1 cell proliferation and IgM and IL-5 production. Moreover, IL-33-activated B1 cells from WT mice could adoptively transfer enhanced CS in ST2(-/-) mice challenged with IL-33. Thus, we demonstrate, to the best of our knowledge, a hitherto unrecognized mechanism of B1 cell activation and IL-33 function, and suggest that IL-33 may play an important role in delayed-type hypersensitivity.
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, United Kingdom.
Mousa
M
Komai-Koma
Derek S
DS
Gilchrist
Andrew N J
AN
McKenzie
Carl S
CS
Goodyear
Damo
D
Xu
Foo Y
FY
Liew
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007075:Immunoglobulin M / Q000096:biosynthesis; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000096:biosynthesis; D007378:Interleukins / Q000008:administration & dosage / Q000009:adverse effects / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D010081:Oxazolone / Q000008:administration & dosage / Q000031:analogs & derivatives; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D015415:Biomarkers; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D007075:Immunoglobulin M; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; D018123:Receptors, Interleukin; D010081:Oxazolone; C040284:2-styryl-4-ethoxymethylene-5-oxazolone