Age-associated changes in Epstein-Barr virus-induced human lymphocyte autoantibody responses

In the present investigation we have studied the capacity of the Epstein-Barr virus (EBV), a ubiquitous human B lymphocyte polyclonal activator, to induce cultured peripheral blood lymphocytes from umbilical cords, young adults (20 to 40 yr old), and elderly adults (75 to 90 yr old) to form IgM antibodies to human IgG or human thyroglobulin. The EBV preparation used was shown to exert its B cell stimulatory effect independently of T cell-suppressor effects. The cultures were studied in limiting dilution analyses, and the data were taken to represent relative numbers of B cell precursors of autoantibody-forming cells in the 3 age groups. The results showed: 1) the EBV-inducible IgM anti-IgG and anti-thyroglobulin-producing cells increased in number from birth to old age; 2) the rise occurred at different times of life for the 2 autoantibodies, anti-IgG reactive B cells increasing between birth and young adulthood, and anti-thyroglobulin reactive B cells between young adulthood and old age; 3) the apparent relative avidity of the anti-IgG for antigen was higher in the elderly adults than in the younger adults. We believe these findings are determined by differences in the frequencies of the respective self-reactive B cells in the circulation. What physiologic or environmental factors determine the differential expansions of the human autoreactive B lymphocytes for IgG and thyroglobulin are not known. It seems possible that individual variations in the sizes of these pools may be a factor in determining susceptibility to autoimmune disease.