Regulatory idiotopes / Constantin A. Bona.

  • Bona, Constantin A.
Date:
[1987], ©1987
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Regulatory idiotopes / Constantin A. Bona. Source: Wellcome Collection.

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    1.1. GENES ENCODING IMMUNOGLOBULIN RECEPTOR 7 terminal transferase, which may also result in increasing the diversity of the im¬ mune receptor. Pollak et al. (1984) have shown that the presence of an extra- nucleotide condon (TAC) at the D-Jn gene junction led to the loss of the GB4-10 regulatory idiotope on a monoclonal anti-PC antibody without altering the ability to bind the antigen. Finally, the somatic mutational events also play an important role in the gen¬ eration of antibody diversity. Their role in the generation of antibody diversity was envisioned already by Bumet (1959) and was later developed into the so¬ matic mutation theory (Weigert et al. 1970). According to this theory, there are only a few germ line genes and the majority of antibody specificities result from somatic mutational events that occur in particular hot spots of the variable re¬ gions of heavy and light chains, namely the hypervariable regions (complemen¬ tary determinant regions). The occurrence of somatic mutations was related to specific events during lymphocyte differentiation (Brenner and Milstein 1966). Sequencing of the preferentially used V^21 light chain in anti-PR8 hemag¬ glutinin monoclonal antibodies originating from a unique fusion allowed the con¬ struction of a pedigree of clones activated during the secondary response in an individual BALB/c mouse. This elegant study demonstrated the sequential accu¬ mulation of mutations during clonal expansion, providing data for a formal demonstration of somatic mutations. Gearhart and Bogenhagen (1983), studying the sequence of IgG anti-phosphocholine (PC) monoclonal antibodies, found clusters of mutations within both the 3'- and 5'-flanking regions of Vh region. Sequencing of monoclonal antibodies specific for arsonate (Margolies et al. 1983) and PR8 influenza virus hemagglutinin (McKean et al. 1984) indicates that each was different from every other and numerous mutations in complemen¬ tary determining regions (CDRs) and framework were observed. However, it should be mentioned that despite numerous mutations observed in the arsonate system (accumulation of mutation during the proliferation of clones producing anti-PR8 or anti-PC antibodies), these events did not alter the antibody specificity or even their binding activity. A single clear-cut example indicating a slight alteration of the specificity by somatic mutation was provided by a study carried out by Cook et al. (1982), who studied the binding activity of in vitro variants obtained from the PC-binding S107 myeloma protein. A variant that differs in Vh amino acid sequence at only a single position (residue 35) lost the ability to bind PC-protein conjugates but not the ability to bind PC itself and acquired the ability to bind to DNA. The control of the expression of Ig genes, like other eukaryotic genes, in¬ volves DNA sequences called enhancers, which increase the transcription from