iNKT cells regulate B cell development and homeostasis in the periphery

Invariant natural killer T (iNKT) cells trans‐activate B cells. We found that this activation caused different fates of different B cell subsets. In the presence of activated iNKT cells, splenic follicular B cells proliferated and expanded whereas the proportion of marginal zone B (MZB) cells was selectively reduced. The reduction in MZB cells was via their activation induced cell death and suppression of proliferation in the presence of iNKT cells. To further understand the role of iNKT cells in peripheral B cell development, we analyzed immature B cells in iNKT cell‐KO and Tg mice as well as in Rag1 −/− mice reconstituted with T and B cells. We found that the proportion of AA4.1 + IgM + transitional immature B cells was increased by 2‐3‐fold in Jα18 −/− and CD1d −/− mice as compared to the WT and Vα14 Tg mice. In resonance with this, the proportion of immature B cells particularly the T2 fraction was reduced in WT and Vα14 Tg mice, but not in Jα18 −/− and CD1d −/− mice, in the presence of activated iNKT cells both in vivo and in vitro. Activation of iNKT cells also reduced the proportion of immature B cells in reconstituted Rag1 −/− mice in vivo. Finally, activated iNKT cells reduced the proportion of MZB cell precursors (T2‐MZP) and up‐regulated CXCR5 expression on MZB cells. In summary, we propose that iNKT cells play an important role in the development and maturation of MZB cells, thus regulating their homeostasis in the periphery. Supported in part by NIH and Arthritis Foundation Southern California Chapter