Biased over-expression of CD4− natural killer T cells induces the expansion of marginal zone B cells in aged Vα14 TCR transgenic C57BL/6 mice

Abstract

Marginal zone B (MZB) cells play an important role in the host defense against blood-borne pathogens. Recently, it has been reported that MZB cells amplify dendritic cell-mediated activation of natural killer T (NKT) cells, suggesting that MZB cells are required for optimal NKT cell stimulation. Prior studies have led us to test whether the increased levels of NKT cells would have an immunological impact on MZB cells. To this end, we employed Vα14 TCR transgenic (tg) mice and found that MZB cells were 2 to 3 times more abundant in these mice, compared with wild-type mice, at 15 weeks of age. In addition, this expansion of MZB cells was not observed in young (5-week-old) Vα14 TCR tg mice, implying that aging is one of the factors regulating MZB cell expansion. Because NKT cells consist of heterogeneous subsets with distinct immunological functions, we next examined whether there were any alterations to the frequencies of individual NKT subpopulations. Interestingly, Vα14 TCR tg mice manifested a biased increase in levels of CD4− NKT cells. These cells are known to produce IFNγ, which may explain the unexpected expansion of MZB cells in Vα14 TCR tg mice, because IFNγ has been reported to activate MZB cells to produce IL10. Taken together, our results demonstrate that the specific increase in numbers of CD4− NKT cells may contribute to MZB cell expansion.