NF-kappa B p50/p65 affects the frequency of Ly49 gene expression by NK Cells

In mice, acquisition of Ly49 receptors characterizes one of the developmental stages of NK cells. We previously described a novel Ly49 promoter, Prol, involved in Ly49 gene regulation in immature NK cells. Prol transcriptional activity requires a NF-kappa B binding site; however, only NF-kappa B/p50 binding to this element was observed. Cotransfection of NF-kappa cB/p65 with Ly49g Prol in LNK cells induced a decrease in the transcriptional activity of the core promoter. Moreover, decreasing NF-kappa B/p65 protein expression by RNA interference increases Prot transcriptional activity. A high rate of NF-kappa B/p65 degradation in LNK cells correlates with Prol activity, since treatment with the proteasome inhibitor MG132 increased levels of NF-kappa B/p65 protein and decreased Prol activity. In addition, analysis of the Ly49 repertoire in NF-kappa B/p50 null mice reveals a decrease in the proportion of NK cells expressing a given Ly49 molecule. The defect in Ly49 expression is observed in the bone marrow and the spleen with a similar altered pattern of developmental stages in each tissue. The frequency of Ly49 expression in NF-kappa B/p52 null mice is slightly increased, indicating the specific role of NF-kappa B/p50 in Ly49 gene activation. These results suggest that NF-kappa B p50/p65 plays a major role in the initiation of Ly49 gene expression in NK cells.

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