T cell development in B cell-deficient mice. V. Stopping anti-mu treatment results in Igh-restricted expansion of the T suppressor cell repertoire concomitant with the development of normal immunoglobulin levels.

Abstract

B cell-deficient (anti-mu-treated) mice have proven to be a valuable tool with which to examine the influence of Ig idiotypic determinants upon the development of the Ts repertoire. We have previously reported that ABA-specific Ts repertoires matured in normal and Ig-deficient environments differ from one another in their composition, and consequently, their functionally expressed Igh restrictions. The present report characterizes the impact of natural development of mature B cell activity upon the composition of the Ts repertoire. After stopping anti-mu treatment of C.AL-20 mice, ABA-specific Ts repertoires undergo a defined expansion shown by their acquisition of an additional Ts network that displays Igh restrictions characteristic of normal C.AL-20 mice. This Igh-1d-restricted repertoire can be readily shown within 2 wk of major increases in surface Ig spleen cells and total serum Ig levels in these mice. At the same time, the original Ts restriction specificity (Igh-1a-restricted) generated in the Ig-deficient environment of anti-mu. C.AL-20 mice, is not lost for at least 20 wk. The resulting dual Ts repertoire, characterized by expression of parallel, idiotypically restricted Ts networks, is demonstrable for at least 13 wk. These findings favor an important role for Ig determinants in determining the makeup of the T cell repertoire, and ultimately, the composition of immunologic networks as a whole.