Somatic generation of antibody diversity.

Hybridization of lambda-mRNAs to excess liver DNA yielded results compatible with gene reiteration frequencies of three or less. Purified mRNA from tumors producing structurally different lambda chains were used in competition hybridization experiments. An unlabeled lambda-mRNA competed with another, labelled mRNA to the same extent as homologous unlabelled lambda-mRNA. Mouse DNA was digested with Eco R-I restriction endonuclease and fractionated by gel electrophoresis. A DNA fragment carrying the V lambda-gene(s) was indentified in this digest. This fragment hybridized with lambda-mRNAs coding for two different lambdaV regions equally well. These results indicate that base sequence homology among lambda-mRNAs is so high that any lambda-mRNA should cross-hybridize with all or most of germ line V lambda genes. From amino acid sequence data, it is argued that there are probably more than 25 different lambdaV regions. Hence it is concluded that the number of germ line genes is too small to account for the diversity of lambda chains.