DNA repair, antibody diversity, and aging

Proposed relationships of DNA repair, mutation, and the process of generation of antibody diversity allow new insights into the mechanism of aging. Pathways of antibody development are reviewed with special attention to steps which generate diversity. The normal process of combinatorial fusion of V region gene segments (i.e. V, D, and J) coding for the entire V region, plus the somatic variation within the fusing sites, appear to be enough to account for adequate antibody diversity without a hypermutation mechanism. We propose that the somatic hypermutation commonly observed in antibody V regions may have limited usefulness to expand the diversity of the antigen-binding capacity of the individual. Rather, such mutation may serve as a time clock for aging. Knowledge about humans with specific abnormal repair and/or mutation functions will allow testing of this proposal.