Antibody Formation

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Abstract
The reviewer emphasizes the persistence of the antigenic determinants over long periods of time, their indispensability for continued antibody formation, and concludes that they act as templates for the formation of complementary combining groups in antibody molecules formed by any competent cell. Although the original form of the "clonal selection theory", which claimed formation of each type of antibody in selected cells only, has been abandoned by its proponents, selective action on a subcellular level as in the selection between ribosomes cannot yet be excluded. The principal objection against selective action is based on the formation of antibodies against artificial synthetic determinants. It is not yet known whether the small differences in the amino acid composition of different antibodies involve the combining groups of these antibodies or whether they are merely a consequence of the heterogeneity of the two antibody populations. Changes in conformation, which lead to complementarity of the combining groups of the antibody, could be the result of interference of the antigenic determinant with the last phase of antibody biosynthesis, the folding of the peptide chains. However, the antigen might also affect the transcription of the nucleotide code into the amino acid sequence and thus change the amino acid sequence in the peptide chains of the antibody molecules. Many biochemists adhere at present to the view that the conformation of a peptide chain is determined by its amino acid sequence. The reviewer believes that the reverse action might take place to a certain extent and that in the presence of an antigenic determinant the tendency to assume a complementary conformation may be so strong that it affects the normal assembly of the amino acids and thus causes deviations from the normal amino acid sequence. The same result would be accomplished by selection on the molecular level, that is, by the selection of only those gamma-globulin molecules which can form complementary combining groups. Interference may occur in two or more of these phases. The difference between the primary and secondary response is quantitative rather than qualitative and depends on the nature of the antigen, the nature of the cell which it penetrates and the enhancement of penetration by adjuvants. The reviewer believes that the inability of an organism to produce antibodies against its own proteins, as in any case of antibody formation, is caused by an excess of antigen in the sites of antibody formation. The lag or induction period between injection or reinjection of the antigen and appearance of detectable antibody may be caused by the same factor.