Germ line basis for antibody diversity

Each antibody polypeptide chain is the product of a gene pair comprising one constant (C) gene coding for that portion of the chain common to all chains of the same type and one variable (V) gene coding for the sequence unique to each chain. Previous evidence indicates that the haploid genome has a single copy of each distinct C gene and that for expression a gene pair is formed with any one of a family of V genes present in the same haploid genome. Hybridization of purified mRNA coding for immunoglobulin heavy chain (mRNA-H) with a vast excess of DNA confirms the existence of a single C gene of each type and multiple V genes. A large number (of the order of 104) of V genes would be consistent with the hybridization results. This suggests considerable V gene redundancy which is a predictable property of a multiple V gene family maintained by expansion and contraction mechanisms. The mRNA-H used in these hybridization studies was isolated by a specific interaction with immunoglobulin. The same method has also been used to isolate a nuclear precursor of mRNA-H. Identification of this precursor strengthens the evidence for the direct joining of the V and C gene pair at the DNA level prior to transcription.