B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo.
Highly regulated activation of B cells is required for the production of specific antibodies necessary to provide protection from pathogen infection. This process is initiated by specific recognition of antigen through the B cell receptor (BCR), leading to early intracellular signaling followed by the late recruitment of T cell help. In this study we demonstrate that specific BCR uptake of CD1d-restricted antigens represents an effective means of enhancing invariant natural killer T (iNKT)-dependent B cell responses in vivo. This mechanism is effective over a wide range of antigen affinities but depends on exceeding a tightly regulated avidity threshold necessary for BCR-mediated internalization and CD1d-dependent presentation of particulate antigenic lipid. Subsequently, iNKT cells provide the help required for stimulating B cell proliferation and differentiation. iNKT-stimulated B cells develop within extrafollicular foci and mediate the production of high titers of specific IgM and early class-switched antibodies. Thus, we have demonstrated that in response to particulate antigenic lipids iNKT cells are recruited for the assistance of B cell activation, resulting in the enhancement of specific antibody responses. We propose that such a mechanism may operate to potentiate adaptive immune responses against pathogens in vivo.
Barral
Patricia
P
Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Eckl-Dorna
Julia
J
Harwood
Naomi E
NE
De Santo
Carmela
C
Salio
Mariolina
M
Illarionov
Petr
P
Besra
Gurdyal S
GS
Cerundolo
Vincenzo
V
Batista
Facundo D
FD
D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005699:Galactosylceramides / Q000276:immunology; D007114:Immunization; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D011947:Receptors, Antigen, B-Cell