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 d riven by antigen interaction with BCR. To study how signaling and anti gen presentation through BCR depend on antigen/BCR affinity, lysozyme- specific B cell transfectants were challenged with mutated lysozymes d iffering in their binding kinetics. For detectable triggering, the ant igen/BCR complex needed a K-a > 10(6) M-1 (dissociation half-life > si milar to 1 s). Mutated lysozymes whose binding was below this threshol d 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-l ife) increased. However, a plateau was reached at K(a)s > similar to 1 0(10) M-1 (dissociation half-life > 0.5 hr), supporting the idea of a ceiling to affinity maturation.