After analyzing the x-ray crystal structures of the germ line antibody-hapten complex before and after maturation, the researchers found that the mature antibody had a 30,000 times greater affinity for hapten than the initial germ line antibody. This greatly increased affinity of the mature antibody for hapten occurred as the result of a small number of somatic point mutations in the variable region of the DNA that codes for the antibody. These mutations of the DNA each involve just a single base on the DNA strand. The mutations occur after the antibody has recognized the antigen, has undergone the initial germ line DNA recombination of the variable region, and has bound to the antigen. |
It was originally thought that the germ line recombination of variable sequences of DNA was the primary step that allowed antibodies to recognize and bind to a wide variety of foreign antigens. (See Nature, Volume 302, April 14, 1983, “Somatic Generation of Antibody Diversity.”) The results of this experiment suggest that post-germ line somatic point mutations play a much greater role in antibody-antigen binding than previously thought. The binding potential of a specific antibody is greatly expanded by the ability of germ line antibodies to undergo further mutation and adopt more than one combining-site configuration. The results imply that there is an entirely new level of antigen recognition that takes place after the germ line antibody has bound to its antigen, and that this new level of recognition significantly increases the binding potential and effectiveness of the antibody. |