title: Requirement of B cells for generating CD4+ T cell memory.
abstract: 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.
authors.affiliation: Department of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. whitmire@scripps.edu
authors.forename: Jason K
authors.initials: JK
authors.lastname: Whitmire
authors.forename: Mary S
authors.initials: MS
authors.lastname: Asano
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
authors.forename: Surojit
authors.initials: S
authors.lastname: Sarkar
authors.forename: Lynn G
authors.initials: LG
authors.lastname: Hannum
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology*