Antibody affinity maturation in selectively bred high and low-affinity mice

Abstract

The affinity of serum antibodies produced by selectively bred lines of mice [high affinity, low affinity, low nonmaturing (N/M)] injected with T-dependent [human serum albumin (HSA), dinitrophenylated bovine gamma-globulin (DNP-BGG)] and T-independent (DNP-Ficoll) antigens in saline and adjuvant has been determined. The lines of mice differ significantly in the affinity of antibody produced to T-dependent antigens injected in saline but not to the T-independent antigen. Unlike mice of the high and low-affinity lines, low-affinity N/M mice failed to show affinity maturation to HSA and DNP-BGG injected in Freund's incomplete adjuvant. However, low-N/M mice responded to DNP-Ficoll injected in adjuvant by the production of antibody of affinity comparable to that produced in the other lines and with a similar maturation in affinity. Carrier priming resulted in the suppression of anti-hapten antibody affinity in all lines but low-N/M mice showed significantly greater suppression late in the response to challenge. Low doses of cyclophosphamide produced a significant increase in affinity in low-N/M mice. These results suggest that the failure of low-N/M mice to show affinity maturation results from increased suppressor T cell activity. The availability of the selectively bred mice provides a useful model for the detailed study of the cellular basis of the control of antibody affinity maturation.