Affinity dependence of the B cell response to antigen: A threshold, a ceiling, and the importance of off-rate

Initiation and affinity maturation of the humoral immune response is driven by antigen interaction with BCR. To study how signaling and antigen presentation through BCR depend on antigen/BCR affinity, lysozyme-specific B cell transfectants were challenged with mutated lysozymes differing in their binding kinetics. For detectable triggering, the antigen/BCR complex needed a K-a > 10(6) M-1 (dissociation half-life > similar to 1 s). Mutated lysozymes whose binding was below this threshold could nevertheless be presented if complexed with soluble antibody. Above the threshold, the concentration of antigen required to trigger a response decreased as the affinity (particularly dissociation half-life) increased. However, a plateau was reached at K(a)s > similar to 10(10) M-1 (dissociation half-life > 0.5 hr), supporting the idea of a ceiling to affinity maturation.