CD1d-restricted help to B cells by human invariant natural killer T lymphocytes.
Invariant natural killer T (NKT) cells are a highly conserved subset of T lymphocytes expressing a semi-invariant T cell receptor (TCR), which is restricted to CD1d and specific for the glycosphingolipid antigen alpha-galactosylceramide. Their ability to secrete a variety of cytokines, which in turn modulate the activation of cells of both innate and acquired immune responses, suggests that invariant NKT cells exert a regulatory role mainly via indirect mechanisms. A relevant question is whether invariant NKT cells can directly help B cells. We document here that human invariant NKT cells are as efficient as conventional CD4+ Th0 lymphocytes in promoting proliferation of autologous memory and naive B lymphocytes in vitro, and in inducing immunoglobulin production. Help to B cells by invariant NKT cells is CD1d-dependent and delivered also in the absence of alpha-galactosylceramide, suggesting that NKT cells recognize an endogenous ligand presented by CD1d on B cells. The two major subsets of invariant NKT cells, CD4+ and double negative (CD4-CD8-), express comparable levels of CD40 ligand and cytokines, but differ in helper functions. Indeed, both subsets induce similar levels of B cell proliferation, whereas CD4+ NKT cells induce higher levels of immunoglobulin production. These results suggest a direct role for invariant NKT cells in regulating B lymphocyte proliferation and effector functions.
Galli
Grazia
G
IRIS Research Center, Chiron Vaccines, 53100 Siena, Italy.
Nuti
Sandra
S
Tavarini
Simona
S
Galli-Stampino
Luisa
L
De Lalla
Claudia
C
Casorati
Giulia
G
Dellabona
Paolo
P
Abrignani
Sergio
S
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D005699:Galactosylceramides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; D007136:Immunoglobulins