The Promotion of  V Region Hypermutation

Higher organisms have evolved unusual molecular and genetic mechanisms to generate high affinity and highly specific antibodies to a seemingly infinite number of foreign antigens (1). Even though a highly diverse germline encoded antibody repertoire is created, most of the antibodies have low affinities and the organism must find a way to modify those antibodies so that they will bind with high affinity and neutralize viruses and toxins. In mice and humans this is done during the course of the T dependent antibody response by introducing large numbers of point mutations (2) into the variable (V) region genes that encode the antigen binding site. B cells expressing antibodies with amino acid substitutions that result in a higher affinity are selectively stimulated to proliferate and differentiate by antigen and helper T cells and these higher affinity antibodies come to dominate the antibody response (3–...