REDUCED HUMORAL IMMUNE ACTIVITY IN LONG-LIVED OLD MICE - APPROACH TO ELUCIDATING ITS MECHANISMS

Abstract

Spleen cells from young (3-5 mo.) and old (22-27 mo.) mice were assessed in cultures, both in vivo and in vitro, for their anti-sheep RBC [red blood cell] response separately and in mixtures. Pooled young spleens, pooled old spleens and individual old spleens were analyzed. The response of pure young spleen cells was always higher than that of pure old spleen cells (.apprx. 30 times). The responses of mixtures were either less than (i.e., reduced; frequency .apprx. 65%), comparable to (i.e., additive; frequency .apprx. 10%), or greater than (i.e., elevated; frequency .apprx. 30%) the sum of the responses given by equivalent numbers of pure young and pure old spleen cells. The reduced response was observed in mixtures containing cells from histologically normal old spleens, old spleens with tumors and old spleens with atrophic follicles. Additive and elevated responses were observed only in mixtures containing cells from histologically normal old spleens. The reduced response is explicable in terms of excessive numbers of suppressor cells in old spleens that can prevent young immunocompetent cells from responding maximally to the test antigen. The additive response can be accounted for by a reduction in number of immunocompetent cells in old spleens and/or a decrease in their functional efficiency. The elevated response can be explained by a reduction in number of at least 1 type of immunocompetent cell in old spleens that exists in excess in young spleens. There are several types of cellular changes responsible for the decrease in humoral immune activity in old mice. Pooling of old spleens, as was commonly done in the past, should be discouraged. Not only might it selectively favor the expression of old spleens with an excess of supressor cells but it conceivably could result in an elevated response.