Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent
type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional
T cells; for IgG production through the same process, however, a second signal is required. Previous
studies have reported that invariant natural killer T (iNKT) cells may be responsible for the
second signal involved in IgG production. In the present study, we addressed whether human iNKT
cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of
human iNKT cells, CD4+ CD8β- (CD4) and CD4- CD8β- [double negative (DN)] cells, were generated
from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag,
induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production
and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production
by CD19+CD27- (na？ve) and CD19+CD27+ (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells; nevertheless, IgM production by both B cell subsets was similarly
reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may
preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.
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