Low affinity antibody production in mice – a form of immunological tolerance?

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Abstract
Inbred mice differ in the relative affinity (KR) of specific antibody produced following four once‐weekly injections of human serum albumin (HSA) in saline. However, KR is high in all strains if the HSA is injected in Freund's complete adjuvant (FCA). Experiments were carried out to determine whether the low KR antibody responses of some mouse strains following immunization with HSA in saline were due to a form of immunological tolerance. Mice of strains which produce low KR antibody to HSA in saline (B 10.D2new and SWR/J) and strains which produce high KR antibody (Ajax and Simpson) were immunized by four once‐weekly injections of 1 mg HSA in saline and challenged with HSA in FCA.Preimmunized “low KR” mice produced low KR antibody on challenge, whereas non‐preimmunized low KR mice produced high KR antibody on challenge. “High KR” mice produced high KR antibody on challenge even when preimmunized. The low KR response to challenge in preimmunized low KR mice was shown to be a result of delayed maturation of affinity and that the inability to produce high KR antibody in response to challenge persists for at least 9 weeks. These results suggested that the preimmunization of low KR strains had resulted in some form of immunological tolerance in which high affinity cells were unable to respond to the challenge of antigen in FCA.Furthermore, following multiple injections (three injections a week for four weeks) of 10 μg or 5 mg of HSA in saline, antibody levels are significantly reduced in both high KR and low KR strains: KR is markedly reduced in the low KR strain and enhanced in the high KR strain.These data are interpreted as providing evidence that interstrain differences in KR are due to greater susceptibility of high affinity cells in low KR strains to tolerance induction than the corresponding cells in high KR strains.