Department of Microbiology and Immunology, University of Nevada, Reno, Reno, Nevada.
Biol Blood Marrow Transplant. 2013 Oct;19(10):1446-52. doi: 10.1016/j.bbmt.2013.07.021. Epub 2013 Jul 31.
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 CB6F1 (H-2(bxd)) hybrid mice express two different alleles for Ly49G receptor, Ly49G(B6) and Ly49G(BALB). We found that CB6F1 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 Pro1 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.
抑制性自然杀伤 (NK) 细胞受体特异性识别主要组织相容性复合体 I (MHC-I) 分子，包括小鼠中的 Ly49 受体和人类中的杀伤免疫球蛋白样受体 (KIR)。“许可”或“武装”模型表明，在 NK 细胞发育过程中，这些受体与自身 MHC-I 分子的结合可使 NK 细胞对癌症和病毒感染更敏感。我们最近报道称，造血干细胞移植 (HSCT) 可诱导功能成熟的 Ly49G(+) NK 细胞的快速和优先扩增，但不会通过 Ly49-MHC-I 相互作用诱导其他 Ly49 家族 NK 细胞的扩增。我们现在扩展这些研究，使用具有不同 MHC-I 单倍型的小鼠来评估两种 Ly49G 受体同工型 Ly49G(B6) 和 Ly49G(BALB)的表达，这些小鼠表达一种或两种同工型。CB6F1 (H-2(bxd)) 杂交小鼠的 NK 细胞表达 Ly49G 受体的两个不同等位基因，即 Ly49G(B6) 和 Ly49G(BALB)。我们发现 CB6F1 小鼠的 Ly49G(B6+) NK 细胞比 Ly49(BALB+) NK 细胞多，并且只有 Ly49G(B6+) NK 细胞在相对数量和 Ly49G 平均荧光强度值方面在 HSCT 后增加，类似于 B6 亲本株。我们进一步观察到，具有相同背景基因的 BALB/c (H-2(d)) 和 BALB.B (H-2(b)) 小鼠中的 Ly49G(+) NK 细胞在 HSCT 后恢复缓慢，而 B6 (H-2(b)) 受者中的 Ly49G(+) NK 细胞则恢复迅速。两个等位基因之间 Pro1 启动子活性的差异与 Ly49G(B6) 相对于 Ly49G(BALB) 的表达差异有关。因此，我们得出结论，在表达该等位基因的品系中，HSCT 后 Ly49G(B6) 受体主导 NK 细胞上的 Ly49G 表达。数据表明，特定 Ly49 家族成员的 Ly49 等位基因多态性可能会根据受者的背景基因而不是 MHC-I 单倍型而对 HSCT 后 NK 细胞的恢复产生不同的影响。
