Autoantibody Idiotypy and Neonatal B Cell Repertoire

Abstract

During ontogeny, antibody variable (V) regions are subjected to selection events at the level of B-cell clones bearing on their surfaces Ig molecules useful to the developing organism. Antigenic determinants of immunoglobulin V regions (idiotypes) are believed to play an essential role in molecular recognition and immune responsiveness to exogenous and self antigens. Recent data indicate that reactivity with self-antigens is prevalent within the natural neonatal repertoire, suggesting that self-antigens are involved in the selection and shaping of the immunologic repertoire. One implication of the above considerations is that V regions having regulatory idiotypes are borne preferentially on antibodies that react with self-antigens. Here, we report on the molecular characterization of the idiotype 62 expressed by BALB/c autoantibodies to a classic self-antigen, thyroglobulin. We show that under appropriate experimental conditions, Id62 can modulate the autoantibody response through a process requiring the activation of regulatory T cells. We also demonstrate that self-reactive V regions bearing Id62 are present in newborn mice and report on the primary structure of the V-region genes encoding Id62. Lastly, we provide evidence that hybridomas derived from unstimulated splenocytes of normal neonatal BALB/c mice express Ig molecules that react prevalently with self-antigens.