What process contributes to 'affinity maturation' of antibodies over time?

Affinity maturation is the process through which the binding affinity of antibodies for their specific antigens increases over time, particularly after a primary immune response. This process primarily involves somatic hypermutation. During somatic hypermutation, mutations are introduced at a high rate into the variable region of immunoglobulin genes in activated B cells. These mutations result in the generation of a diverse range of antibody variants that have different affinities for the antigen.

B cells that have undergone somatic hypermutation and produced higher-affinity antibodies are selected for in a process called affinity competition. Those B cells with mutations that improve affinity will outcompete others for binding to the antigen and receive survival signals, leading to their proliferation. This selective process results in a higher overall affinity of the antibody response as the immune system adapts to the antigen.

While allelic exclusion ensures that each B cell expresses only one specificity of antibody and VDJ recombination is crucial for the initial generation of diverse antibody specificities, they do not play a direct role in the gradual increase of affinity over time. Isotype switching allows B cells to change the class of antibody they produce without altering the antigen specificity, but it does not involve the mutation process that enhances affinity. Therefore, somatic hypermutation is the