Somatic Mutations of Immunoglobulin Variable Genes are Restricted to the Rearranged V Gene

An important question concerning the mechanism of somatic mutation of immunoglobulin variable (V) genes is whether it involves all of the numerous V genes in a differentiated B cell, independent of location, or if it is restricted to a particular chromosomal site. Comparison of the sequence of two alleles of a given V gene shows that the mutations are limited to the rearranged V gene, while the same V gene on the other chromosome has not undergone mutation. This indicates that a V gene sequence alone is not sufficient for somatic mutation to take place. The mutation is therefore restricted to the rearranged V gene and consequently does not occur before rearrangement.