Pivotal advance: eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production.
Alum, aluminum-hydroxide-containing compounds, long used as adjuvants in human vaccinations, functions by ill-defined, immunostimulatory mechanisms. Antigen-free alum has been shown to act via a previously unidentified, splenic Gr1(+), IL-4-expressing myeloid cell population to stimulate early B cell priming. We demonstrate that the alum-elicited and -activated splenic myeloid cells are IL-4-expressing eosinophils that function to prime B cell responses. Eosinophils are the principal Gr1(+), IL-4(+) cells in the spleens 6 days following i.p. alum administration. Alum-elicited splenic B cell priming, as evidenced by MHC II cross-linking-mediated calcium mobilization developed in wild-type BALB/c mice, was absent in DeltadblGATA BALB/c eosinophil-deficient mice and could be reconstituted by adoptive eosinophil infusions into the eosinophil-deficient mice. Moreover, early antigen-specific IgM antibody responses in alum-antigen-immunized mice were impaired in eosinophil-deficient mice and were restored with adoptive transfers of eosinophils. Thus, eosinophils, leukocytes of the innate immune system that contain preformed cytokines, including IL-4, have novel, immunomodulatory roles in the initial priming of B cells elicited by the adjuvant alum and in the optimal early B cell generation of antigen-specific IgM.
Wang
Hai-Bin
HB
Department of Medicine, Harvard Medical School, Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Boston MA, 02215, USA.
Weller
Peter F
PF
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019264:Adoptive Transfer; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002118:Calcium / Q000502:physiology; D004804:Eosinophils / Q000276:immunology* / Q000502:physiology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D002118:Calcium