Invariant NKT cells sustain specific B cell responses and memory.
Invariant natural killer T (iNKT) cells are innate-like lymphocytes recognizing CD1d-restricted glycolipid antigens, such as alpha-galactosylceramide (alphaGC). We assessed whether iNKT cells help B lymphocyte responses and found that mice immunized with proteins and alphaGC develop antibody titers 1-2 logs higher than those induced by proteins alone. Activation of iNKT cells enhances protection against infections such as influenza and elicits higher frequencies of memory B cells and higher antibody responses to booster immunizations. Protein vaccination with alphaGC, but not with conventional adjuvants, elicits IgG responses in mice lacking MHC class II molecules, demonstrating that iNKT cells can substitute for CD4(+) T cell help to B cells. Interestingly, the decay of circulating antibodies is faster in mice lacking iNKT cells. These findings point to a homeostatic role for iNKT cells on critical features of the antibody response such as immunity and B cell memory.
Galli
Grazia
G
Novartis Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Pittoni
Paola
P
Tonti
Elena
E
Malzone
Carmine
C
Uematsu
Yasushi
Y
Tortoli
Marco
M
Maione
Domenico
D
Volpini
Gianfranco
G
Finco
Oretta
O
Nuti
Sandra
S
Tavarini
Simona
S
Dellabona
Paolo
P
Rappuoli
Rino
R
Casorati
Giulia
G
Abrignani
Sergio
S
D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000378:metabolism* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005699:Galactosylceramides / Q000378:metabolism; D007107:Immune System; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology; D013997:Time Factors
D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; C493154:alpha-galactosylceramide