Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene.
- 1 July 1979
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 76 (7) , 3450-3454
- https://doi.org/10.1073/pnas.76.7.3450
Abstract
Mouse immunoglobulin [Ig] .kappa. chain gene formation involves site-specific somatic recombination between one of several hundred germ-line variable region genes and a joining site (J segment) encoded close to the constant [c] region gene. The nucleotide sequence of major portions of the recombination region of the mouse .kappa. gene was determined and cloned and a series of 5 such J segments spread out along a segment of DNA 2.4 kilobases from the .kappa. constant region gene was discovered. These J segments encode the 13 COOH-terminal amino acids of the variable region, probably including amino acids involved in the antigen combining site and in H/L chain contacts. The J segments also display striking sequence homology to one another in both their coding and immediately flanking sequences. Major elements of a short palindrome.sbd.CAC .**GRAPHIC**. GTG.sbd.are preserved adjacent to the recombination sites of both variable and J region genes and constitute inverted repeats at both ends of the sequences to be joined. These palindromes can be written as a hypothetical stem structure that draws variable and J regions together, providing a possible molecular basis for the DNA joining event. Four of the J segments that were discovered encode amino acid sequences already found in myeloma proteins. By altering the frame of recombination, additional L chain amino acid sequences can be accounted for suggesting that the V[variable]/J joining event might generate antibody diversity somatically both by using different combinations of V and J region genes and by using alternative joining frames.Keywords
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