title: Cognate interaction with iNKT cells expands IL-10-producing B regulatory cells.
abstract: Successful induction of B-cell activation and memory depends on help from CD4+ T cells. Invariant natural killer T (iNKT) cells (glycolipid-specific, CD1d-restricted innate lymphocytes) provide both cognate (direct) and noncognate (indirect) helper signals to enhance B-cell responses. Both forms of iNKT-cell help induce primary humoral immune responses, but only noncognate iNKT-cell help drives humoral memory and plasma cells. Here, we show that iNKT cognate help for B cells is fundamentally different from the help provided by conventional CD4+ T cells. Cognate iNKT-cell help drives an early, unsustained germinal center B-cell expansion, less reduction of T follicular regulatory cells, an expansion of marginal zone B cells, and early increases in regulatory IL-10-producing B-cell numbers compared with noncognate activation. These results are consistent with a mechanism whereby iNKT cells preferentially provide an innate form of help that does not generate humoral memory and has important implications for the application of glycolipid molecules as vaccine adjuvants.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983;
authors.forename: Emilie E
authors.initials: EE
authors.lastname: Vomhof-DeKrey
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yates
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden;
authors.forename: Thomas
authors.initials: T
authors.lastname: Hägglöf
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983;
authors.forename: Paula
authors.initials: P
authors.lastname: Lanthier
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983;
authors.forename: Eyal
authors.initials: E
authors.lastname: Amiel
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Natacha
authors.initials: N
authors.lastname: Veerapen
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden;
authors.forename: Mikael C I
authors.initials: MC
authors.lastname: Karlsson
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983; leadbetter@UTHSCSA.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Leadbetter
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; D006017:Glycolipids; D016753:Interleukin-10
keywords: B regulatory cells; IL-10; iNKT cells; iNKT follicular helper cells; marginal zone B cells