NFATc1 and NFATc2 together control both T and B cell activation and differentiation

NFAT transcription factors play critical roles in gene transcription during immune responses. To investigate further the two most prominent NFAT famil y members, NFATc1 and NFATc2, we generated mice bearing lymphoid systems de void of both. Doubly deficient T cells displayed cell surface markers of ac tivation yet were significantly deficient in the development of multiple ef fector functions, including Th cytokine production, surface effector molecu le expression, and cytolytic activity. Nevertheless, doubly deficient B cel ls were hyperactivated, as evidenced by extremely elevated serum IgG1 and I gE, as well as plasma cell expansion and infiltration of end organs. Thus, in T cells, NFATc1 and NFATc2 are dispensable for inflammatory reactivity b ut are required for effector differentiation, while in B cells, NFATs regul ate both normal homeostasis and differentiation.