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 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.
Batista
F D
FD
Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom.
Neuberger
M S
MS
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D002460:Cell Line; D008081:Liposomes / Q000276:immunology; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D000941:Antigens; D008081:Liposomes; D011947:Receptors, Antigen, B-Cell