The studies supported by NIA grant investigated the immunochemical characteristics of human anti-Gamma globulin antibodies. During the course of these studies we delineated a new category of antibodies designated as """"""""epibodies"""""""", which are specific for idiotypes but secondarily bind to human FcGamma. In animal models, we have found that the age-dependent occurrence of anti-IgG antibodies in 129/Sv and MRL/1pr mice is associated with a variation in clones responding to T-independent antigens, as well as with the classes of antibodies elicited during a secondary immmune response. Interestingly, we have found that in aged animals, regardless of whether or not they were prone to develop disease, rheumatoid factors normally occurred during immune responses elicited by conventional antigens. We proposed that the production of such anti-Gamma globulin antibodies can be beneficial, a defense mechanism, aiding in the clearance of infectious agents, particularly when a decrement of T cell functions occur during aging. Based on these results, we propose to continue this program by studying: 1. The immunochemical properties and molecular basis of rheumatoid factors monoclonal antibodies obtained from aged 129/Sv mice and from normal mice immunized with conventional antigens. 2. T cell clones specific for rheumatoid factors and the cellular mechanisms responsible for the occurrence of autoanti-IgG antibodies. 3. The regulatory function of rheumatoid factors on immune responses. 4. The effects of rheumatoid factors on the defense mechanisms against influenza virus infection in young and old animals 5. The effect of anti-Id antibodies specific for rheumatoid factors during the aging process An understanding of immunochemical properties of rheumatoid factors, of their molecular basis and functional properties in young and aged animals will aid in evaluating their beneficial or deleterious effects during aging.
|Bona, C A (1988) Genes regulating rheumatoid factors. Springer Semin Immunopathol 10:57-65|
|Manheimer-Lory, A J; Monestier, M; Bellon, B et al. (1986) Fine specificity, idiotypy, and nature of cloned heavy-chain variable region genes of murine monoclonal rheumatoid factor antibodies. Proc Natl Acad Sci U S A 83:8293-7|