Ly49 and CD94/NKG2 receptor acquisition by NK cells does not require lymphotoxin-β receptor expression

Abstract

AbstractA crucial step in murine natural killer (NK) cell development, mediated by bone marrow stromal cells, is the induction of Ly49 and CD94/NKG2 receptor expression. The signals that regulate Ly49 receptor expression are still largely undetermined. It has been shown that interaction between lymphotoxin α1β2 (LTα1β2) and LTβ receptor (LTβR), expressed on lymphoid progenitor cells and nonlymphoid bone marrow stromal cells, respectively, is important for both quantitative and functional NK cell development. Therefore, we have investigated the role of LT-LTβR–mediated signaling in Ly49 and CD94/NKG2 receptor acquisition. We show that the NK receptor repertoire of LTβR–/– mice can only be partially analyzed because of the residual 129/Ola mouse genetic background, due to a physical linkage of the LTβR locus and the loci encoding the Ly49 and CD94/NKG2 receptors. Therefore, we transferred wild-type B6 lymphoid-committed progenitor cells into LTβR–/– mice, which differentiated into NK cells with a normal NK cell receptor repertoire. Also, administration of LTβR-immunoglobulin (Ig), which acts as a soluble receptor for LTα1β2, resulted in reduced NK cell percentages but did not influence the Ly49 and CD94/NKG2 receptor acquisition on remaining NK cells. These results indicate that LTβR-mediated signals are not required for Ly49 and CD94/NKG2 receptor acquisition.