Effect of age on the expressed B cell repertoire: role of B cell subsets

Aged humans and experimental animals are impaired in their responsesto most foreign antigens although they produce greater amountsof autoantibodies. We have examined the effect of age on theproduction of antibodies to a prototypic foreign antigen, sheeperythrocytes (SRBC), and to a prototypic autoantigen, bromelain-treatedmouse erythrocytes (BrMRBC), in young and old ice before andafter immunization with SRBC. Old mice express more anti-BrMRBCplaqueforming cell (PFC) antibodies before and an even greaternumber after immunization with SRBC than young mice. Conversely,old mice produce far fewer anti-SRBC PFC than young mice followingimmunization with SRBC. We hypothesized that the differencesin the responses of old mice to BrMRBC and SRBC reflects differencesin the activity of CD5⁺ and CD5^– B cells. To test thishypothesis we immunized young and old mice with foreign antigensreported (and confirmed in our studies) to stimulate CD5⁺ Bcells TNP-ficoll and phosphorylcholine - keyhole limpet hemocyanln(KLH)] or CD5^– B cells (SRBC and TNP-KLH). We found thatthe PFC response of old mice to antigens mediated by CD5⁺ Bcells was equal to or greater than that of young mice. In contrastthe PFC response of old mice induced by antigens mediated byCD5⁺ B cells was only 10% that of young mice. Thus it appearsthat the immune response of old mice is well maintained forantigens which elicit a CD5⁺ B cell response but not for thosewhich elicit a CD5^– B cell response. This conclusion issupported by our finding that a higher percentage of splenicB cells from old compared to young mice express that V_H11 lghgene family. This V_H gene family is preferentially expressedby CD5⁺ B cells.