Immunoglobulin VH gene expression in human aging.

Area of Science:

• Immunology
• Gerontology
• Molecular Biology

Background:

• Immune responses undergo significant alterations with advancing age.
• The impact of aging on the expressed B cell repertoire, specifically immunoglobulin heavy chain (Ig VH) gene usage, remains incompletely understood.

Purpose of the Study:

• To investigate age-associated changes in the expressed B cell repertoire in humans.
• To compare Ig VH cDNA libraries from elderly and young adults to identify differences in gene expression and mutation patterns.

Main Methods:

• Analysis of Ig VH cDNA libraries derived from circulating B cells of elderly and young human adults.
• Utilized single-cell RT-PCR in two elderly individuals to validate findings and assess potential bias toward activated cells in library analysis.

Main Results:

• Nearly two-thirds of B cell clones in both age groups exhibited minimal V(H) mutations, indicating continued production of naive B cells.
• A notable increase in V(H)4 family gene expression was observed in elderly subjects, contrasting with the predominant V(H)3 family expression in young adults.
• While individual variation was higher in the elderly, both cDNA library analysis and single-cell RT-PCR showed similar V(H) family usage patterns.

Conclusions:

• Aging humans maintain the capacity to generate naive B cells with unmutated Ig genes.
• A shift towards increased utilization of V(H)4 family members in the elderly suggests altered selection processes during B cell development prior to antigen-driven affinity maturation.