Ly49 And Cd94/Nkg2 Receptor Acquisition By Nk Cells Does Not Require Lymphotoxin-Beta Receptor Expression

A 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 alpha(1)beta(2) (LT alpha(1)beta(2)) and LTP receptor (LTPR), 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-LT beta R-mediated signaling in Ly49 and CD94/ NKG2 receptor acquisition. We show that the NK receptor repertoire of LT beta R-/mice can only be partially analyzed because of the residual 129/Ola mouse genetic background, due to a physical linkage of the LTPR locus and the loci encoding the Ly49 and CD94/NKG2 receptors. Therefore, we transferred wild-type B6 lymphold-committed progenitor cells into LT beta R-/- mice, which differentiated into NK cells with a normal NK cell receptor repertoire. Also, administration of LTPR-immunoglobulin (1g), which acts as a soluble receptor for Milk 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 LTPR-mediated signals are not required for Ly49 and CD94/NKG2 receptor acquisition.