Dysregulation of the humoral immune response in old mice

The increase in autoantibodies with age of both experimentalanimals and humans has been thought to reflect a shift in theantibody repertoire from foreign to self antigens. In mice,before immunization, the age-associated increase in antibodiesreactive with a prototypic autoantigen, bromelain-treated autologouserythrocytes (BrMRBC), reflected a 3-fold increase in serumIgM and the number of IgM-secreting spleen cells in old comparedwith young mice. However, the percentage of the IgM-secretingspleen cell repertoire reactive with BrMRBC in old mice wasactually {small tilde}50% that in young mice. In contrast, afterimmunization with sheep erythrocytes (SRBC), old mice showeda 5-fold increase in the percentage of IgM-secreting cells reactivewith BrMRBC while young mice showed no significant increase.The converse is true for the percentage of IgM-secreting spleencells in old mice specific for SBRC, which is 10% the numbergenerated by young mice. The increased autoantibody responseof old mice is not, however, linked to their poor response tothe nominal antigen. Thus, immunization with phosphorylcholine(PC) conjugated Keyhole limpet hemocyanin, an antigen that inducesa comparable anti-PC response in old and young mice, also inducedmore autoantibody forming cells in old than young mice. Theincreased autoantibody response of old mice after immunizationcan be accounted for by both an increased number of Ig-secretingspleen cells as well as an increased percentage of the expressedrepertoire of IgM-secreting spleen cells that react with autoantigens.In contrast, prior to immunization the age-associated increasein serum autoantibodies and autoantibody-secreting spleen cellscan be accounted for by the increased concentration of serumIg and the polyclonal activation of splenic B cells.