Published online before print January 11, 2008

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(Journal of Leukocyte Biology. 2008;83:817-821.)
© 2008 by Society for Leukocyte Biology

Pivotal Advance: Eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production

Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

¹ Correspondence: Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Medicine, Divisions of Allergy and Inflammation and Infectious Diseases, DA 617, 330 Brookline Avenue, Boston MA, 02215, USA. E-mail: pweller{at}bidmc.harvard.edu

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 dblGATA 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.

Key Words: BALB/c • MHC II • innate immunity

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