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 5 MURINE Vh LOCUS 36-09 36-60 X24 J606 J558 SI07 QPC52 7183 Ш Ш CE] Ш ® Ш И ПЛ-р Figure 1.1 Order of V gene families on murine Ун locus. digested fragments of genomic DNA with various Vh probes, they divided these 100 Vh genes into seven families. A similar classification of murine genes was proposed by Dildrope (1984) after a computer analysis of protein or DNA sequences of about 100 antibodies. Genes within a family exhibit more than 80% sequence homology. The Vh gene family is located in the following order start¬ ing from the 5' end of the Vh locus on chromosome 12: VhX24, VuJóOó, Vh36-60, VhJ558, V^SIO?, V^QPCSl, and VuMOPCll (Fig. 1.1). The size of the Vh families varies widely. Thus, whereas the VnJ558 family is composed of about 60 genes, the VhX24 family is composed of only two Vh genes. An important mechanism that contributes to the antibody diversity of the Ig receptor is the combinatorial pairing of heavy and light chains. This process is necessary to produce a functional immune receptor since the hypervariable re¬ gions of both variable regions of the heavy and light chains make up the walls of the combining site. This was well documented by affinity labeling experiments (Haimovitch et al. 1972), as well as by spectrographic studies of Fab crystals (Segal et al. 1974). Evidence for supporting the role of heavy-light chain shuf¬ fling in increasing the antibody repertoire comes from the analysis of Vh and Vl chains used by antibodies with various specificities. Thus, whereas the pairing of V^IO light chain with Vh 36-65 gives an arson- ate-specific antibody, V^IO light chain with Vh deriving from the Vh441-4 germ line genes gives antibodies specific for ß2-6-fructosan, and with V^OXl gives an oxazalone-binding Ig. Similarly, VhJ606 in association with V^ll in BALB/c mice gives antibodies specific for ß2-l-fructosan whereas in association with Vxl in A/J mice it gives antibodies specific for Л^-acetylglucosamine (Ra¬ bat et al. 1983). These two examples clearly illustrate that the combinatorial pairing of Vh and Vl chains represents an important element for the diversity of the immune receptor of В cells. The estimation of the number of V genes carried out by using various methods showed that there are a few Vx and about 100 V^ and Vh germ line genes. How¬ ever, the random joining of V J segments of Vl and of V-D-J of Vh regions that occurs during the differentiation of the В lineage represents an important source