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J Leukoc Biol. 2008 Apr;83(4):817-21. doi: 10.1189/jlb.0607392. Epub 2008 Jan 11.

Pivotal advance: eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production.

Author information

1
Department of Medicine, Harvard Medical School, Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Boston MA, 02215, USA.

Abstract

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.

PMID:
18192490
PMCID:
PMC2735468
DOI:
10.1189/jlb.0607392
[Indexed for MEDLINE]
Free PMC Article

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