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

The immune response to phosphocholine in BALB/c mice involves one group of heavy chain variable region (VH) genes and at least three groups of light 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 six amino acids. We have isolated several closely related V region genes of immunoglobulin light chains from a mouse sperm DNA phage library, selecting clones that cross-hybridize with a cDNA plasmid probe encoding the light chain of MOPC 167. We identified six strongly hybridizing clones, representing three separate cloning events. We determined the sequence of the coding and immediate flanking regions of three clones, representing the three separate cloning events, and they proved to be identical. This germ-line sequence encoded the amino acid sequence of neither MOPC 167 nor MOPC 511, but required four base pair changes to generate the V kappa M167 cDNA sequence and five base pair changes to generate the V kappa M511 gene. By Southern hybridization experiments, we demonstrated that neither MOPC 511 nor MOPC 167 germ-line genes exist. We conclude that the V kappa M167 and V kappa M511 genes are created somatically.