IFN-gamma-dependent and -independent initiation of switch recombination byNK cells

We have examined the effect of IL-2-propagated NK or NK-T cells on each of the steps required for B cell switch recombination leading to IgG2a product ion. The results indicate that NK cells, on their own and in the absence of IFN-gamma, can induce germline transcription in resting, IgG(-) B lymphocy tes from the gamma 2a locus as well as mRNA for activation-induced cytidine deaminase (AID) via a process that requires cell-cell interactions. The re sults also show that, in contrast to induction by T cells, activation by NK cells does not involve CD40-CD40 ligand interactions and does not extend t o the induction of I gamma1 transcription. Furthermore, in contrast to stim ulation by LPS and IFN-gamma or by T cells, the activation events initiated by NK cells do not result in significant synthesis of functional gamma 2a mRNA in resting B lymphocytes even in the presence of IFN-gamma. Thus, indu ction of germline and AID transcripts are necessary but not sufficient even ts for functional switching to IgG2a. These experiments, showing that NK ce lls themselves cannot induce IgG2a production but can polyclonally program B lymphocytes so that they preferentially switch to this isotype may explai n how activated NK cells can skew the Ag-specific immune response toward Ig G2a. The findings also provide further demonstration of the definitive yet limited extent of how a non-Ag-specific component of the innate system can modulate the direction of the adaptive immune response. The Journal of Immu nology, 2001.