Nature 292, 845 - 848 (27 August 1981); doi:10.1038/292845a0

Switch region of immunoglobulin C gene is composed of simple tandem repetitive sequences

Toshio Nikaido, Sumiko Nakai & Tasuku Honjo

Department of Genetics, Osaka University Medical School, Kita-ku, Osaka 530, Japan

Immunoglobulin heavy (H) chain genes comprise a family of variable region (V) genes and several constant region (C) genes which are classified, in mouse, into five major classes: , , , and . During differentiation of a given B lymphocyte, a specific V_H gene is first expressed as a part of the -chain and at a later stage the expressed H chain switches the C region from to or without alteration of the V_H region sequence¹⁻³. This phenomenon, called immunoglobulin class switch, involves a unique recombination event that takes place at the region 5' to each C_H gene during B-lymphocyte differentiation⁴⁻⁶. The regions responsible for the class switch (or S−S) recombination are defined as switch (S) regions⁴. Recent structural analyses, which have revealed that S regions comprise tandem repetition of short unit sequences⁷⁻¹⁰, have allowed us to define the S region on a structural basis. The nudeotide sequences of S regions vary among different classes of C_H gene, inevitably raising the possibility that the S sequence contains separate subsets of sequences, each of which may pair with the S region of a different class. To test this possibility it is necessary to characterize the whole S region. However, because the -gene clones isolated by other groups^5,11,12 have lost a major portion (3 kilobases [kb]) of the central core of the S region, only a small part of the S region sequence has been determined^8,10,12,13. We have now characterized the complete S region by nudeotide sequence determination and restriction enzyme cleavage, and have found that it comprises simple tandem repetition of two kinds of 5-base pairs (bp) unit sequences, GAGCT and GGGGT. The nudeotide sequence of the S region shares short common sequences with all the other S-region sequences. The results clearly exclude the above-mentioned possibility and support the proposal^7,9,10,13 that S−S recombination is mediated by repetitive homologous short sequences.

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