Somatic diversification is required to generate the V kappa genes of MOPC 511 and MOPC 167 myeloma proteins.

Abstract

The immune response to phosphocholine in Balb/c mice involves 1 group of H chain variable region (VH) genes and at least 3 groups of L chain variable region (V.KAPPA.) genes, represented by the gene products of the myelomas TEPC 15, MOPC 603 and MOPC 167/MOPC 511. The amino acid sequences of BALB/c myeloma .KAPPA. chains MOPC 167 and MOPC 511 are known and they differ by 6 amino acids. Several closely related V region genes of Ig L chains were isolated from a mouse sperm DNA phase library and clones that cross-hybridize with a c[complementary]DNA plasmid probe encoding the L chain of MOPC 167 were selected. Six strongly hybridizing clones, representing 3 separate cloning events, were identified. The sequence of the coding and immediate flanking regions of 3 clones, representing the 3 separate cloning events, proved to be identical. This germ-line sequence encoded the amino acid sequence of neither MOPC 167 nor MOPC 511, but required 4 base pair changes to generate the V.KAPPA.M167 cDNA sequence and 5 base pair changes to generate the V.KAPPA.M511 gene. Southern hybridization experiments demonstrated that neither MOPC 511 nor MOPC 167 germ-line genes exist. Evidently, the V.KAPPA.M167 and V.KAPPA.M511 genes are created somatically.