title: T cell-independent restimulation of FVIII-specific murine memory B cells is facilitated by dendritic cells together with toll-like receptor 7 agonist.
abstract: Memory B cells are involved in long-term maintenance of antibody-dependent immunologic disorders. Therefore, it is essential to understand how the restimulation of FVIII-specific memory B cells in hemophilia A with FVIII inhibitors is regulated. We asked whether concurrent activation of the innate immune system by an agonist for toll-like receptor (TLR) 7 is able to facilitate the differentiation of FVIII-specific memory B cells in the absence of T-cell help. TLR7 recognizes single-stranded RNA as contained in RNA viruses such as influenza, Sendai, and Coxsackie B viruses. Our results indicate that highly purified murine memory B cells do not differentiate into FVIII-specific antibody-secreting cells in the presence of FVIII and the TLR7 agonist when cultured in the absence of CD4(+) T cells. However, CD11c(+) dendritic cells facilitate the T cell-independent differentiation of FVIII-specific memory B cells but only in the presence of FVIII and the TLR7 agonist. In contrast to T cell-dependent restimulation, the antibody response after T cell-independent restimulation of FVIII-specific memory B cells is skewed toward IgG2a, an antibody subclass that is efficient in activating the complement system and in inducing Fc-receptor-mediated effector functions, both are required for effective immune responses against pathogens.
authors.affiliation: Baxter BioScience, Vienna, Austria.
authors.forename: Aniko G
authors.initials: AG
authors.lastname: Pordes
authors.forename: Christina K
authors.initials: CK
authors.lastname: Baumgartner
authors.forename: Peter
authors.initials: P
authors.lastname: Allacher
authors.forename: Rafi U
authors.initials: RU
authors.lastname: Ahmad
authors.forename: Markus
authors.initials: M
authors.lastname: Weiller
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Schiviz
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Schwarz
authors.forename: Birgit M
authors.initials: BM
authors.lastname: Reipert
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D000939:Epitopes / Q000187:drug effects / Q000276:immunology; D005169:Factor VIII / Q000276:immunology*; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013379:Substrate Specificity / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D051199:Toll-Like Receptor 7 / Q000819:agonists*
chemical_list: D000939:Epitopes; D051199:Toll-Like Receptor 7; D005169:Factor VIII