Diversity of the Ig repertoire is maintained with age in spite of reduced germinal centre cells in human tonsil lymphoid tissue

Humans and almost all species studied to date exhibit a decreased responsiveness to immunization and increased autoimmunity with age. While this has been observed clinically for decades, only recently has an understanding of the molecular basis for these changes begun to be appreciated. Studies of the B-cell aspects of these changes in ageing mice and the very few reports in ageing humans have not been conclusive. Here we examine the nucleotide sequence of over 1250 VH transcripts from the tonsils of individuals of various ages for changes to the VH4 immunoglobulin repertoire. An exhaustive examination of VH, DH and JH gene segment utilization revealed a remarkable similarity of the repertoires. The extent of somatic hypermutation was fully maintained or even increased by some measures into the eighth decade of life. However, we found by middle age that the representation of naive and germinal centre B-cell subpopulations changed relative to total B lymphocytes in the tonsil. While the percentage of naive and germinal centre B-cell subpopulations changes during the second half of life, these findings suggest that even with advancing age, humans remain capable of generating an extremely diverse Ig repertoire while maintaining a similar spectrum of Ig rearrangements once the germinal centre reaction begins.