AGE-RELATED-CHANGES IN ANTIBODY REPERTOIRE - CONTRIBUTION FROM T-CELLS

The immune system of aged mice produces antibodies that are characteri zed by low affinity, diminished protection against infections and auto reactivity. It has been shown that these antibodies may be encoded by different immunoglobulin V genes and that the mechanism of somatic hyp ermutation in the V genes is inefficient. Studies on scid mice reconst ituted with B and T cells from donors of different ages suggested that both lymphocyte subsets may contribute to the age-related changes in antibody repertoire. With help provided by T cells from young mice, th e response to a hapten, nitrophenyl(acetyl), became gradually dominate d by B-cell clones that rearranged a particular germline V-H gene (V18 6.2). However, help from the aged T cells resulted in a heterogeneous response of B cells expressing many different V segments. Analysis of discrete foci of primary antibody-forming cells suggested that the age d T-helper cells are unable to govern the normally-occurring competiti on between the B-cell clones that have different affinities for the ha pten. It is proposed that a signaling disequilibrium from the aged T c ells, which provide less efficient help in quantitative terms, support s the growth of low-affinity B cells. This process may be exacerbated due to the apparent hyperactivity of aged B cells to CD40-mediated mit ogenic signal.