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A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen¹

Fredrik Hjelm^*, Mikael C. I. Karlsson and Birgitta Heyman^2,*

^* Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; and Department of Medicine, Karolinska Institute, Clinical Allergy Research Unit, Stockholm, Sweden

Ag administered i.v. to mice along with specific IgE or IgG2a induces higher Ab- and CD4⁺ T cell responses than Ag administered alone. The IgE effect is completely dependent on the low-affinity receptor for IgE, CD23, whereas the IgG2a effect depends on activating FcRs. In vitro studies suggest that IgE/Ag is presented more efficiently than Ag alone to CD4⁺ T cells by CD23⁺ B cells and that IgG2a/Ag is presented by FcR⁺ dendritic cells (DCs). In this study, we investigate in vivo the early events leading to IgE- and IgG2a-mediated enhancement of immune responses. OVA administered i.v. in PBS in combination with specific IgE binds circulating B cells after 5 min and is found in B cell follicles bound to follicular B cells (CD23^high) after 30 min. This novel B cell-dependent route of entry is specific for IgE because IgG2a-Ag complexes were trapped in the marginal zone. OVA-specific CD4⁺ T cells were found at the T-B border in the T cell zones 12 h after immunization both with IgE/OVA or IgG2a/OVA and proliferated vigorously after 3 days. The findings suggest that IgE- and IgG2a-immune complexes are efficient stimulators of early CD4⁺ T cell responses and that Ag bound to IgE has a specific route for transportation into follicles.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Uppsala University, the Swedish Research Council, Ellen, Walter and Lennart Hesselman’s Foundation, Hans von Kantzow’s Foundation, King Gustaf V’s 80 Years Foundation, and Ollie and Elof Ericsson’s Foundation.

² Address correspondence and reprint requests to Dr. Birgitta Heyman, Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123, Uppsala, Sweden. E-mail address: birgitta.heyman{at}imbim.uu.se

³ Abbreviations used in this paper: GC, germinal center; TNP, 2,4,6-trinitrophenyl; FDC, follicular dendritic cell; DC, dendritic cell; HEL, hen egg lysozyme; FO, follicular; MZ, marginal zone; PNA, peanut agglutinin.