Immunoglobulin VH Gene Expression in Human Aging

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 1999-11, Vol.93 (2), p.132-142
• Main Authors: Wang, Xiaowei, Stollar, B.David
• Format: Article
• Language: English
• Subjects: Adult; Aged; aging; Aging - genetics; Aging - immunology; B cell; Biological and medical sciences; cDNA library; DNA, Complementary - chemistry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation - immunology; Gene Frequency; Gene Library; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Genes, Immunoglobulin - genetics; Humans; Ig repertoire; Immunobiology; Immunoglobulin Heavy Chains - biosynthesis; Immunoglobulin Heavy Chains - genetics; Immunoglobulin J-Chains - biosynthesis; Immunoglobulin J-Chains - genetics; Immunoglobulin Variable Region - biosynthesis; Immunoglobulin Variable Region - genetics; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Molecular Sequence Data; Mutation - genetics; Mutation - immunology; Protein Structure, Tertiary - genetics; Reverse Transcriptase Polymerase Chain Reaction; single cell PCR; VH domain
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1006/clim.1999.4781

Immune responses change in aging humans, but it is not known whether there is an age-associated change in the expressed B cell repertoire. We compared Ig VH cDNA libraries from circulating B cells of five elderly and three young human adults. As in young persons, nearly two-thirds of the cDNA clones from older subjects had zero to three VH mutations, although there was more individual variation among the elderly. VH4 family expression increased in older subjects, both in unmutated and in mutated cDNA clones, whereas VH3 family expression predominated in young adults. To test for bias toward activated cells in the cDNA libraries, we studied two older persons by both cDNA library analysis and single-cell RT-PCR. In one subject, more than 85% of VH segments were unmutated by either analysis. In the second, mutated Ig segments were much more frequent in cDNA clones than in consecutive single cells; however, VH family usage and high representation of particular genes were similar in both analyses. While aging humans continue to produce naive B cells with unmutated Ig genes, a shift to greater use of the VH4 family members and expression of particular genes may reflect changes in selection of developing B cells before affinity maturation toward reactivity with foreign antigen.