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Immunity. 1998 Jun;8(6):751-9.

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

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Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom.


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 Ka > 10(6) M(-1) (dissociation half-life > approximately 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 Kas > approximately 10(10) M(-1) (dissociation half-life > 0.5 hr), supporting the idea of a ceiling to affinity maturation.

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