Correlation between immune maturation and idiotypic network recognition

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Abstract
The maturation of T‐dependent humoral immune responses is mediated by somatic mutations. Antigen selection is one mechanism for the activation of B cell clones which express antibodies with progressively increased affinity and which are derived as somatic variants from germ‐line‐encoded genes. However, the emergence of B cell clones secreting rather low‐affinity antibodies and the shift to alternative germ‐line V region gene combinations during secondary and tertiary responses cannot be explained by antigen selection. It has been considered that idiotypic suppression may favor this clonal shift. Such an involvement would require that idiotypic recognition in the syngeneic host must be highly restricted to private idiotopes of each clone sequentially activated during immune maturation. To test this possibility, we produced 19 syngeneic anti‐idiotypic antibodies to the germ‐line‐encoded major Ox1 idiotype (IgM‐IdOx1 H11.5) of the anti‐2‐phenyl‐oxazolone (phOx) immune response in BALB/c mice. The fine specificity of these anti‐IdOx1 was tested with a set of anti‐phOx monoclonal antibodies, representing the first steps of maturation. About half of the anti‐IdOx1 showed almost no reactivity with the IdOx1 after the switch to IgG and none of the anti‐IdOx1 reacted with anti‐phOx antibodies which carried a glycine or histidine instead of arginine as the middle amino acid of the D region. These observations suggest a strong correlation between immune maturation and the idiotypic network. A model is presented in which idiotypic suppression may function as a driving force for diversification and maturation of the antigen‐induced immune response.