NKT-cell help to B lymphocytes can occur independently of cognate interaction.
CD4(+) T (Th)-cell help to B lymphocytes requires cognate interaction and CD40 engagement. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that recognize alphagalactosylceramide (alphaGalCer) presented by CD1d, and can help B-cell responses. We asked whether alphaGalCer-activated iNKT cells help B lymphocytes through cognate interaction, or indirectly, via enhancement of Th-B-cell interaction. After immunization with protein Ags and alphaGalCer, antibody titers were assessed in wild-type or splenectomized mice, and in bone marrow radiation chimeras lacking CD1d or CD40 expression on B lymphocytes, or expressing CD1d or MHC II disjointly on antigen-presenting cells (APCs). We find that alphaGalCer-dependent enhancement of B-cell response (1) can occur when B cells do not express CD1d but express CD40; (2) requires that iNKT and Th cells interact with the same APCs that coexpress both CD1d and MHC-II; and (3) takes place without spleen. These findings demonstrate alphaGalCer-induced help for antibody responses can occur without cognate iNKT/B-cell interaction, and suggest this help entails activation of APCs by iNKT cells, which in turn activate Th cells and their helper functions for B cells. Thus, the alphaGalCer-induced help recapitulates the function of classical adjuvants that stimulate the innate immune system to support adaptive immune responses.
Tonti
Elena
E
Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, DIBIT, H. San Raffaele Scientific Institute, Milano, Italy.
Galli
Grazia
G
Malzone
Carmine
C
Abrignani
Sergio
S
Casorati
Giulia
G
Dellabona
Paolo
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000502:physiology*; D017951:Antigen Presentation / Q000187:drug effects / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D005699:Galactosylceramides / Q000276:immunology* / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology*; D007114:Immunization; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D055610:Antigens, CD1d; D019013:CD40 Antigens; D005699:Galactosylceramides; D000949:Histocompatibility Antigens Class II; C493154:alpha-galactosylceramide