Nucleotide sequences of switch regions of immunoglobulin C epsilon and C gamma genes and their comparison.

Abstract

Immunoglobulin class switch involves a unique recombination event that takes place at the switch (s) region which is located 5' to each constant region (C) gene of the heavy (H) chain.For example, differentiation of the B lymphocyte from a p-chain producer to an €-chain producer is mediated by the switch recombination between the S, and S. regions.In order to elucidate the molecular mechanism for the switch recomb& nation, we have determined nucleotide sequences surrounding the class switch recombination sites of the C, and C,S genes and those in the 5' flanking regions of the CYz, and CS genes.The results indicate that the 5' flanking regions of all the CH genes except for the C8 gene contain the S regions which comprise tandem repetition of short unit sequences in agreement with the previous analyses of the SJ, Sy2b, S , and S, regions.Comparison of the nucleotide sequences of all the S regions revealed that length as well as nucleotide sequences of the S regions vary among different classes of the CH gene, but they share short common sequences, (G)AGCT and TGGG(G).The nucleotide sequence of the S, region is homologous to those of the other S regions in the decreasing order of the S,, So, Sy3, and (S71, S,2b, Sr2a) regions.We have compared the nucleotide sequences immediately adjacent to the recombination sites of seven rearranged genes and have always found tetranucleotides TGAG and/or TGGG, except for one case.Such tetranucleotides may constitute a part of the recognition sequence of a putative recombinase.These results provide further support for our previous proposal that the switch recombination may be facilitated by short common sequences dispersed in all the S regions.The antibody molecule contains two different polypeptide chains, light and heavy chains, each comprising the variable region which determines antigen-binding specificity and the constant region which mediate biologicd effector functions such as complement fixation.The immunoglobulin is divided into five major classes, IgM, IgD, IgG, IgE, and IgA, which are defined by their H' chain constituents, p, 6, y, E, and a, respectively.During differentiation of a single B lymphocyte, a given VH gene is first expressed as a part of the p chain.