Type I IFN enhances follicular B cell contribution to the T cell-independent antibody response.
Humoral immunity to viruses and encapsulated bacteria is comprised of T cell-independent type 2 (TI-2) antibody responses that are characterized by rapid antibody production by marginal zone and B1 B cells. We demonstrate that toll-like receptor (TLR) ligands influence the TI-2 antibody response not only by enhancing the overall magnitude but also by skewing this response to one that is dominated by IgG isotypes. Importantly, TLR ligands facilitate this response by inducing type I interferon (IFN), which in turn elicits rapid and significant amounts of antigen-specific IgG2c predominantly from FO (follicular) B cells. Furthermore, we show that although the IgG2c antibody response requires B cell-autonomous IFN-alpha receptor signaling, it is independent of B cell-intrinsic TLR signaling. Thus, innate signals have the capacity to enhance TI-2 antibody responses by promoting participation of FO B cells, which then elaborate effective IgG anti-pathogen antibodies.
Swanson
Cristina L
CL
Integrated Department of Immunology, University of Colorado, Denver, CO 80206, USA.
Wilson
Timothy J
TJ
Strauch
Pamela
P
Colonna
Marco
M
Pelanda
Roberta
R
Torres
Raul M
RM
D000818:Animals; D000915:Antibody Affinity / Q000187:drug effects / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D000939:Epitopes / Q000187:drug effects / Q000276:immunology; D005362:Ficoll / Q000494:pharmacology; D017578:Immunoglobulin Class Switching / Q000187:drug effects / Q000276:immunology; D016898:Interferon-alpha / Q000494:pharmacology*; D007700:Kinetics; D037181:Lectins, C-Type / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011070:Poly I-C / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D000099192:CD69 Antigens
D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000939:Epitopes; D005362:Ficoll; D016898:Interferon-alpha; D037181:Lectins, C-Type; D011070:Poly I-C; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D051196:Toll-Like Receptor 3; D000099192:CD69 Antigens; C406563:IgG2c receptor; C519703:TLR3 protein, mouse