Switch recombination and somatic hypermutation at the immunoglobulin heavy chain locus. (a) The murine heavy chain locus (left) has undergone VDJ recombination and encodes a μ heavy chain. The resulting IgM antibodies (right) are pentamers of a dimer containing two heavy and two light chains. (b) Class switch recombination joins a new constant region to the expressed variable (VDJ) region, resulting in synthesis of antibody of a new class. Shown is switch recombination from Cμ to Cγ1, to produce a dimeric IgG1 antibody (right). (c) Somatic hypermutation modifies the variable region sequences of both heavy chains (left) and light chains. Following affinity selection, hypermutated antibodies (right) have increased affinity for antigen. Stars denote mutations in the DNA (left) and protein (right). Somatic hypermutation is shown following switch recombination, but neither process is prerequisite for the other (see text for further details). VDJ, heavy chain variable region; S, switch region; C, constant region.