IMMUNOGLOBULIN HEAVY-CHAIN JUNCTIONAL DIVERSITY IN YOUNG AND AGED HUMANS

The causes of observed deficiencies in the humoral immune response-in aged humans are unknown. Since a major source of antibody diversity is generated at the V-H-D-J(H) junctional regions of the immunoglobulin heavy chain, we determined whether differences in junctional diversity are manifested with aging. We compared the CDR3 regions of IgM heavy chain transcripts isolated from young adult and aged humans. A PCR ass ay that measures CDR3 length in the majority of mu-heavy chains showed the same average size and normal range of CDRS length in aged individ uals as observed in young adults. To characterize the features of junc tional diversity of aged adults in more derail, we determined the CDRS sequences of a subset of the mu-heavy chain repertoire that utilizes members of the V(H)5 family. In general, CDR3 length, D family usage, and J(H) gene usage were similar in aged compared to young adults. Thu s, in contrast to dramatic changes in heavy chain junctional diversity associated with fetal to adult development, no major differences were found between young and aged adults. Since the CDR3 repertoire genera ted in aged individuals appears ro be as diverse as that observed in y ounger adults, the decline in humoral immunocompetence with aging cann ot be attributed to a restriction in heavy chain junctional diversific ation processes. (C) American Society for Histocompatibility and Immun ogenetics, 1997. Published by Elsevier Science Inc.