Generalization of single immunological experiences by idiotypically mediated clonal connections

Abstract

Clonal interactions of B cells by idiotope-specific mutual recognition of their antigen receptors with the participation of T cells were assumed to form a web of unknown density, referred to as the idiotypic network. Although these clonal connections were proposed to fulfill important internal regulatory functions, their biological significance, especially in relation to antigen-induced immune responses, remained a mystery. In view of this, we postulate that the basic function of the idiotypic internal connection between B and T cell antigen receptors is to transform antigen-induced cellular activations, by idiotypic crossreactivity, into the regulation of cell clones with different antigen specificities. This process leads not only to the suppression of major clones but also to the activation of minor ones. The latter activating property may allow the generalization of single antigenic experiences, so that the immune system in its entirety benefits in its battle against environmental microbes. Such idiotypic clonal interactions are particularly effective in early ontogeny. During a short neonatal imprinting period, maternal immunological knowledge in the form of somatically mutated, high-affinity IgG antibodies, acquired through a continuous encounter with external antigens, guides the initial ontogenetic development of the immune system and so exerts long-lasting transgenerational advantageous effects in the offspring.