[Considerations on the origin of the diversity of immunoglobulins (author's transl)]

In spite of the numerous theories proposed to explain the origin of the diversity of immunoglobulins, none can define satisfactorily the nature of the generator of diversity and its mode of action. Even the concept of the variable and constant portions of immunoglobulin chains is no longer valid which opens up the question about the hypothetical existence of the V and C genes. Moreover, phylogenetic considerations strongly suggest that there is a fundamental difference in the mechanism of amino acid substitution for the immunoglobulins and for homologous proteins undergoing normal divergent evolution. A conceptionally and functionally simple mechanism, based on a variable translation of the immunoglobulin mRNA, has been suggested as the generator of diversity (Rev. canad. Biol., 1969, 28, 179). The criteria of this mechanism are (1) the presence of inosine in the mRNA and (2) the existence of a series of overmethylated tRNAs for the selective recognition of inosine-containing codons. Although the experimental proof for this mechanism is still lacking, it cannot be fortuitous that the lack of adenosine deaminase is associated with immune deficiency and that an increased tRNA methylase activity exists in plasmocytomas.