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.

Avidity progression of dietary antibodies in healthy and coeliac children

“…However, this would not explain the increased avidity of anti‐ β ‐lactoglobulin antibodies in coeliac children, as their anti‐ β ‐lactoglobulin antibodies have a subclass pattern similar to that found in healthy children [47]. Finally, there is a possibility that coeliac patients could be inherently predisposed to produce high‐avidity antibodies to dietary antigens, as antibody avidity is genetically influenced [48].…”

Immunopathological mechanisms in the induction of parasitic diseases with particular reference to type III hypersensitivity reactions

“…These non-affinity maturing mice (N/M) have been interbred and show a very marked increase in severity of antigen-antibody complex disease compared to the low-affinity line. The failure to develop normal affinity maturation has been suggested to arise from an increased activity of T-suppressor cells (Steward, Stanley & Furlong, 1986).…”

“…This depression of affinity and delay in affinity maturation of antibody to an antigen unrelated to the parasite may be the result of an antigen-specific process involving suppressor T-cells. There is evidence that T-suppressor cells can suppress normal affinity maturation (Steward et al 1986). The possibility does, however, exist that inefficient selection of high-affinity cells in the presence of polyclonal B-cell activation in infected animals may have led to low-affinity production.…”