Differential Expression of the Ly49GB6, but Not the Ly49GBALB, Receptor Isoform during Natural Killer Cell Reconstitution after Hematopoietic Stem Cell Transplantation

Inhibitory natural killer (NK) cell receptors specific for major histocompatibility complex class I (MHC-I) molecules include Ly49 receptors in mice and killer immunoglobulin-like receptors (KIR) in humans. The "licensing" or "arming" models imply that engagement of these receptors to self MHC-I molecules during NK cell development educates NK cells to be more responsive to cancer and viral infection. We recently reported that hematopoietic stem cell transplantation (HSCT) induced rapid and preferential expansion of functionally competent Ly49G(+), but not other Ly49 family, NK cells independent of NK cell licensing via Ly49 MHC-I interactions. We now extend these studies to evaluate expression of the two Ly49G receptor isoforms Ly49G(B6) and Ly49G(BALB), using mice with different MHC-I haplotypes that express one or both of the isoforms. NK cells from CB6F(1) (H-2(bxd)). j hybrid mice express two different alleles for Ly49G receptor, Ly49G(B6) and Ly49G(BALB). We found that CB6F(1) mice had more Ly49G(B6+) NK cells than Ly49(BALB+) NK cells, and that only Ly49G(B6+) NK cells increased in relative numbers and in Ly49G mean fluorescence intensity values after HSCT similar to the B6 parental strain. We further observed that Ly49G(+) NK cells in BALB/c (H-2(d)) and BALB.B (H-2(b)) mice, which have the same background genes, recover slowly after HSCT, in contrast to Ly49G(+) NK cells in B6 (H-2(b)) recipients. The difference in expression of Ly49G(B6) relative to Ly49G(BALB) was linked to differences in the activity of the Prol promoter between the two alleles. Thus, we conclude that the Ly49G(B6) receptor dominates Ly49G expression on NK cells after HSCT in strains in which that allele is expressed. The data suggest that Ly49 allelic polymorphism within a particular Ly49 family member can differentially affect NK cell recovery after HSCT depending on the background genes of the recipient, not on the MHC-I haplotype. (C) 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.