Nf-B p50/p65 Affects the Frequency of Ly49 Gene Expression by Nk Cells

Pascal, V.; Nathan, N.R.; Claudio, E.; Siebenlist, U.; Anderson, S.K.

The Journal of Immunology 179(3): 1751-1759


DOI: 10.4049/jimmunol.179.3.1751
Accession: 068490724

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In mice, acquisition of Ly49 receptors characterizes one of the developmental stages of NK cells. We previously described a novel Ly49 promoter, Pro1, involved in Ly49 gene regulation in immature NK cells. Pro1 transcriptional activity requires a NF-kappaB binding site; however, only NF-kappaB/p50 binding to this element was observed. Cotransfection of NF-kappaB/p65 with Ly49g Pro1 in LNK cells induced a decrease in the transcriptional activity of the core promoter. Moreover, decreasing NF-kappaB/p65 protein expression by RNA interference increases Pro1 transcriptional activity. A high rate of NF-kappaB/p65 degradation in LNK cells correlates with Pro1 activity, since treatment with the proteasome inhibitor MG132 increased levels of NF-kappaB/p65 protein and decreased Pro1 activity. In addition, analysis of the Ly49 repertoire in NF-kappaB/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-kappaB/p52 null mice is slightly increased, indicating the specific role of NF-kappaB/p50 in Ly49 gene activation. These results suggest that NF-kappaB p50/p65 plays a major role in the initiation of Ly49 gene expression in NK cells.