Antibody affinity maturation in selectively bred high and low-affinity mice.
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.
D000276:Adjuvants, Immunologic; D000818:Animals; D000915:Antibody Affinity; D000917:Antibody Formation; D002352:Carrier Proteins / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology; D004140:Dinitrophenols / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007156:Immunologic Memory; D051379:Mice; D012709:Serum Albumin / Q000008:administration & dosage / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D004140:Dinitrophenols; D012709:Serum Albumin; D003520:Cyclophosphamide