SEQUENCES OF 5 POTENTIAL RECOMBINATION SITES ENCODED CLOSE TO AN IMMUNOGLOBULIN K-CONSTANT REGION GENE

Immunoglobulin kappa chain gene formation involves site-specific somatic recombination between one of several hudred germ-line variable region genes and a joining site (or 'J segment') encoded close to the constant region gene. We have cloned and determined the nucleotide sequence of major portions of the recombination region of the mose gene and discovered a series of five such J segments spread out along a segment of DNA 2,4 kilobases from the kappa constant region gene. 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 heavy/light 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 - CAC(T/A) GTG - 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 we have discovered encode amino acid sequences already found in myeloma proteins. By altering the frame of recombination, we can account for additional light chain amino acid sequences, suggesting that the V/J joining event might generate antibody diversity somatically both by using different combinations of variable and J region genes and by using alternative joining frames.