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 α-galactosylceramide (αGC). We assessed whether iNKT cells help B lymphocyte responses and found that mice immunized with proteins and αGC develop antibody titers 1-2 logs hig...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2007-03, Vol.104 (10), p.3984-3989
Main Authors: Galli, Grazia, Pittoni, Paola, Tonti, Elena, Malzone, Carmine, Uematsu, Yasushi, Tortoli, Marco, Maione, Domenico, Volpini, Gianfranco, Finco, Oretta, Nuti, Sandra, Tavarini, Simona, Dellabona, Paolo, Rappuoli, Rino, Casorati, Giulia, Abrignani, Sergio
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Antigens, CD1 - metabolism
Antigens, CD1d
B lymphocytes
B-Lymphocytes - metabolism
B-Lymphocytes - virology
Biological Sciences
CD4-Positive T-Lymphocytes - metabolism
Cellular biology
Galactosylceramides - metabolism
H1N1 subtype influenza A virus
H3N2 subtype influenza A virus
Immune System
Immunization
Immunoglobulins
Immunologic Memory
Killer Cells, Natural - metabolism
Killer Cells, Natural - virology
Lymphocytes
Memory
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Transgenic
Natural killer T cells
Orthomyxoviridae Infections - immunology
Proteins
Rodents
T lymphocytes
Time Factors
Vaccination
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Summary:Invariant natural killer T (iNKT) cells are innate-like lymphocytes recognizing CD1d-restricted glycolipid antigens, such as α-galactosylceramide (αGC). We assessed whether iNKT cells help B lymphocyte responses and found that mice immunized with proteins and αGC 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 αGC, 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0700191104