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.
Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Patricia
P
Barral
Julia
J
Eckl-Dorna
Naomi E
NE
Harwood
Carmela
C
De Santo
Mariolina
M
Salio
Petr
P
Illarionov
Gurdyal S
GS
Besra
Vincenzo
V
Cerundolo
Facundo D
FD
Batista
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