The variability, arrangement, and rearrangement of immunoglobulin genes.

The multiplicity of heavy-chain variable-region (VH) genes in mouse and human DNA has been estimated using a mouse heavy-(H) chain cDNA clone. We found about 10 hybridization components in mouse DNA and about 20 components in human DNA. Cross-hybridization studies of variable region (V) genes indicate that these components represent the numbers of genes within the VH subgroups of each of these species. The arrangement and rearrangement of the H-chain gamma subclasses have been studied in order to assess possible mechanisms of the H-chain switch. Evidence has been found for rearrangement events involving the gamma 2a and gamma 2b constant-region (CH) genes in DNA from cells making IgG2a and IgG2b respectively. In addition we found that cells making IgG2a lack detectable genes for gamma1 and gamma 2b. Both sets of observations are discussed in relation to H-chain diversity and the switch.