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Requirement of B Cells for Generating CD4⁺ T Cell Memory¹

Jason K. Whitmire^2,*, Mary S. Asano, Susan M. Kaech, Surojit Sarkar, Lynn G. Hannum, Mark J. Shlomchik and Rafi Ahmed

^* Department of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA 92037; Emory Vaccine Center and Department of Microbiology & Immunology, Emory University School of Medicine, Atlanta, GA 30322; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520; and Department of Immunobiology and Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510

B cells can influence T cell responses by directly presenting Ag or by secreting Ab that binds to Ag to form immunogenic complexes. Conflicting evidence suggests that persisting Ag-Ab complexes propagate long-term T cell memory; yet, other data indicate that memory cells can survive without specific Ag or MHC. In this study, the roles of B cells and Ag-Ab complexes in T cell responses to lymphocytic choriomeningitis virus (LCMV) infection were investigated using B cell-deficient or B cell-competent mice. Despite normal lymphocyte expansion after acute infection, B cell-deficient mice rapidly lost CD4⁺ T cell memory, but not CD8⁺ T cell memory, during the contraction phase. To determine whether Ag-Ab complexes sustain CD4⁺ T cell memory, T cell responses were followed in B cell-transgenic (mIg-Tg) mice that have B cells but neither LCMV-specific Ab nor LCMV-immune complex deposition. In contrast to B cell-deficient mice, mIg-Tg mice retained functional Th cell memory, indicating that B cells selectively preserve CD4⁺ T cell memory independently of immune complex formation. An in vivo consequence of losing CD4⁺ T cell memory was that B cell-deficient mice were unable to resolve chronic virus infection. These data implicate a B cell function other than Ab production that induces long-term protective immunity.

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¹ This work was supported by National Institutes of Health R-01 Grants AI074862 (to J.K.W.), AI43603 (to M.J.S.), and AI-30048 (to R.A.); Burroughs-Wellcome Fund Grant 1004313 and National Institutes of Health R-01 Grants AI066232-01 and CA038350 (to S.M.K.); an Associate Investigator Award from the Department of Veterans Affairs and a postdoctoral fellowship from the National Multiple Sclerosis Society (to M.S.A.); and National Institutes of Health Training Grant AI07019 and a Richard K. Gershon Predoctoral Fellowship (to L.G.H.).

² Address correspondence and reprint requests to Dr. Jason K. Whitmire, Department of Immunology & Microbial Science, SP3030-2110, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. E-mail address: whitmire{at}scripps.edu

³ Abbreviations used in this paper: FDC, follicular dendritic cell; MHC-II, MHC class II; LCMV, lymphocytic choriomeningitis virus; mIg-Tg, membrane Ig transgenic; NP, 4-hydroxy-3-nitrophenyl acetyl; CTLp, CTL precursor.