Effect of somatic mutation on antibody affinity and specificity

By using antibody-forming cells in culture, it is possible to examine the effect of somatic mutations in the variable-region genes of antibodies in the absence of the selective forces that exist in vivo. Such studies reveal that single amino acid substitutions in the variable region of the heavy chain can lead to loss of antigen binding. An example is given of an important protective antibody against a bacterial antigen that undergoes a point mutation, resulting in loss of antigen binding and acquisition of autoreactivity.