Genetic control of the decline of natural killer cell activity in aging mice.

NK cell activity declines with age and is strain dependent. We investigated the age associated decline of NK cell activity in the HW26C strain of mice. The bilineal congenic strain HW26C which contains a segment of chromosome 4 of BALB/cBy introduced onto the C57BL/6By (B6) background was used to investigate the decline of NK cell activity with age. Our experiments showed that there is a significant decline of NK cell activity in old (18-26 months) HW26C mice as compared to the B6. By contrast, the NK cell frequency determined using a surface marker for NK cells, NK1.1, did not show any significant difference with age. It appears therefore, that the decline in NK activity during aging is a reflection of loss of lytic activity rather than an actual decline in the number of NK cells and the responsible gene(s) resides in chromosome 4.

Role of a genetic region on chromosome 4 in the regulation of natural killer cell activity in mice.

Natural killer cell (NK) activity is regulated by both the H-2 and non-H-2 genes. Using bilineal congenic HW26C and HW13 mice which differ from the background strain C57BL/6By (B6) in a region of chromosome 4, we investigated the role played by a gene/genes in a segment of chromosome 4 of BALB/cBy on NK cell activity. Percoll separated low density spleen cells from young HW26C and HW13 mice showed a 3.5 fold higher NK activity than the B6. We also observed that the increase in NK activity of HW26C was not due to an increase in the number of NK cells. Using five other bilineal congenics containing different regions of chromosome 4 of BALB/cBy, we observed that the putative gene(s) regulating NK activity may be located between b and IFN-alpha/beta genes of chromosome 4. The level of NK activity of (B6xHW26C)F1 ranked between the HW26C and B6 suggesting that the gene product described is inherited in an incompletely dominant fashion.