title: Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses.
abstract: Dendritic cells (DCs) are best known for their ability to activate naive T cells, and emerging evidence suggests that distinct DC subsets induce specialized T cell responses. However, little is known concerning the role of DC subsets in the initiation of B cell responses. We report that antigen (Ag) delivery to DC-inhibitory receptor 2 (DCIR2) found on marginal zone (MZ)-associated CD8α(-) DCs in mice leads to robust class-switched antibody (Ab) responses to a T cell-dependent (TD) Ag. DCIR2(+) DCs induced rapid up-regulation of multiple B cell activation markers and changes in chemokine receptor expression, resulting in accumulation of Ag-specific B cells within extrafollicular splenic bridging channels as early as 24 h after immunization. Ag-specific B cells primed by DCIR2(+) DCs were remarkably efficient at driving naive CD4 T cell proliferation, yet DCIR2-induced responses failed to form germinal centers or undergo affinity maturation of serum Ab unless toll-like receptor (TLR) 7 or TLR9 agonists were included at the time of immunization. These results demonstrate DCIR2(+) DCs have a unique capacity to initiate extrafollicular B cell responses to TD Ag, and thus define a novel division of labor among splenic DC subsets for B cell activation during humoral immune responses.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98195, USA. cpchapp@u.washington.edu
authors.forename: Craig P
authors.initials: CP
authors.lastname: Chappell
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Draves
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Giltiay
authors.forename: Edward A
authors.initials: EA
authors.lastname: Clark
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051217:Toll-Like Receptor 9 / Q000819:agonists
chemical_list: D000941:Antigens; D000939:Epitopes; D007074:Immunoglobulin G; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9