ABSTRACT
The accumulation of somatic mutations correlates with an increase in antibody affinity for the antigen. Thus somatic hypermutation is an important factor in the maturation of the immune response. Assuming that the mutational mechanism operates more or less randomly over the entire variable region of the antibody molecules, many of the mutations will destroy rather than improve the affinity for the antigen. Primary responses in general seem to start from naive B-cell clones whose receptors have not yet been diversified by the hypermutation mechanism. The formation of germinal centers coincides with the time when the genes encoding antibody molecules are diversified by hypermutation and for the reason it was suggested that the microenvironment of the germinal center is necessary to activate the hypermutation mechanism. A preferrential expansion of high-affinity variants would be ensured since such cell lines would not pick up secondary—possibly deleterious—mutations.
