Differential expression of the Ly49GB6, but not the Ly49GBALB, receptor isoform during natural killer cell reconstitution after hematopoietic stem cell transplantation

Isabel Barao, Paul W. Wright, Can M. Sungur, Stephen K. Anderson, Doug Redelman, William J Murphy

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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 Ly49GB6 and Ly49GBALB, using mice with different MHC-I haplotypes that express one or both of the isoforms. NK cells from CB6F1 (H-2bxd) hybrid mice express two different alleles for Ly49G receptor, Ly49GB6 and Ly49GBALB. We found that CB6F1 mice had more Ly49GB6+ NK cells than Ly49BALB+ NK cells, and that only Ly49GB6+ 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-2d) and BALB.B (H-2b) mice, which have the same background genes, recover slowly after HSCT, in contrast to Ly49G+ NK cells in B6 (H-2b) recipients. The difference in expression of Ly49GB6 relative to Ly49GBALB was linked to differences in the activity of the Pro1 promoter between the two alleles. Thus, we conclude that the Ly49GB6 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.

Original languageEnglish (US)
Pages (from-to)1446-1452
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume19
Issue number10
DOIs
StatePublished - Oct 2013

Keywords

  • Hematopoietic stem cell transplantation
  • Ly49G
  • Natural killer cell

ASJC Scopus subject areas

  • Transplantation
  • Hematology

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