Regulation of antibody heterogeneity by suppressor T cells: diminishing suppressor T cell activity increases the number of dinitrophenyl clones in mice immunized with dinitrophenyl-poly(Glu,Lys,Phe) or dinitrophenyl-poly(Glu,Lys,Ala).
The anti-hapten responses to the dinitrophenyl (Dnp) conjugate of the random linear terpolymers poly(L-Glu,LLys,LPhe), GLphi, or poly(LGlu,LLys,LAla), GLA, are of highly restricted heterogeneity. Thus, individual mice of most responder strains express an average of two to four anti-Dnp clones to Dnp-GLphi or Dnp-GLA, as measured by isoelectric focusing techniques. To explore whether suppressor T cells regulate the heterogeneity of the anti-hapten response to Dnp conjugates of these polypeptides, various procedures aimed at reducing suppressor T-cell activity were tested for their ability to alter the restricted isoelectric focusing spectrotypes. These procedures, such as adult thymectomy, administration of low doses of cyclophosphamide, and in vivo treatment with anti-I-J antisera, significantly increased the magnitude and heterogeneity of the anti-Dnp antibody response to Dnp-GLphi and Dnp-GLA in strains of mice that possessed responder Ir genes. Such methods failed to alter the nonresponder status of mice that lacked the appropriate Ir genes. Thus, in systems under Ir gene control suppressor T-cell mechanisms appear to be involved in the regulation of the heterogeneity of hapten-specific B-cell responses.