title: B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation.
abstract: High-affinity class-switched Abs and memory B cells are products of the germinal center (GC). The CD4+ T cell help required for the development and maintenance of the GC is delivered by follicular Th cells (T(FH)), a CD4+ Th cell subset characterized by expression of Bcl-6 and secretion of IL-21. The cellular interactions that mediate differentiation of TFH and GC B cells remain an important area of investigation. We previously showed that MHC class II (MHCII)-dependent dendritic cell Ag presentation is sufficient for the differentiation of a T(FH) intermediate (termed pre-T(FH)), characterized by Bcl-6 expression but lacking IL-21 secretion. In this article, we examine the contributions of MHCII Ag presentation by B cells to T(FH) differentiation and GC responses in several contexts. B cells alone do not efficiently prime naive CD4+ T cells or induce T(FH) after protein immunization; however, during lymphocytic choriomeningitis virus infection, B cells induce T(FH) differentiation despite the lack of effector CD4+ T cell generation. Still, MHCII+ dendritic cells and B cells cooperate for optimal T(FH) and GC B cell differentiation in response to both model Ags and viral infection. This study highlights the roles for B cells in both CD4+ T cell priming and T(FH) differentiation, and demonstrates that different APC subsets work in tandem to mediate the GC response.
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Barnett
authors.forename: Helen M A
authors.initials: HM
authors.lastname: Simkins
authors.forename: Burton E
authors.initials: BE
authors.lastname: Barnett
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Korn
authors.forename: Andy L
authors.initials: AL
authors.lastname: Johnson
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Wu
authors.forename: Terri M
authors.initials: TM
authors.lastname: Laufer
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007114:Immunization; D051379:Mice; D018345:Mice, Knockout; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D006183:H-2 Antigens