CORRELATION BETWEEN IMMUNE MATURATION AND IDIOTYPIC NETWORK RECOGNITION

The maturation of T-dependent humoral immune responses is mediated by somatic mutations. Antigen selection is one mechanism for the activati on of B cell clones which express antibodies with progressively increa sed affinity and which are derived as somatic variants from germ-line- encoded genes. However, the emergence of B cell clones secreting rathe r low-affinity antibodies and the shift to alternative germ-line V reg ion gene combinations during secondary and tertiary responses cannot b e explained by antigen selection. It has been considered that idiotypi c suppression may favor this clonal shift. Such an involvement would r equire 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 syn geneic antiidiotypic antibodies to the germ-line-encoded major Ox1 idi otype (IgM-Id(Ox1) H11.5) of the anti-2-phenyl-oxazolone (phOX) immune response in BALB/c mice. The fine specificity of these anti-Id(Ox1) w as tested with a set of anti-phOx monoclonal antibodies, representing the first steps of maturation. About half of the anti-Id(Ox1) showed a lmost no reactivity with the Id(Ox1) after the switch to IgG and none of the anti-Id(Ox1) reacted with anti-phOx antibodies which carried a glycine or histidine instead of arginine as the middle amino acid of t he D region. These observations suggest a strong correlation between i mmune maturation and the idiotypic network. A model is presented in wh ich idiotypic suppression may function as a driving force for diversif ication and maturation of the antigen-induced immune response.