Kinetic maturation of an immune response.
Is the affinity maturation of antibodies under thermodynamic or kinetic control, or both? We compared the physical constants of hapten binding by antibodies from 2-phenyl-5-oxazolone-specific hybridomas from primary, secondary and tertiary responses. In addition to an increase in equilibrium constant, there was a shift in the antibody repertoire after the primary response towards an immunoglobulin family with an extremely high on-rate constant. This shift occurred in spite of the average or below-average affinity of this group of antibodies. This is consistent with B-lymphocyte proliferation being subject to a kinetic selection, with a premium on binding target antigens rapidly, in parallel with a thermodynamic selection based on binding tightly.
Foote
J
J
MRC Laboratory of Molecular Biology, Cambridge, UK.
Milstein
C
C
D000818:Animals; D005803:Genes, Immunoglobulin; D006241:Haptens; D006825:Hybridomas / Q000276:immunology; D007109:Immunity; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D010081:Oxazolone / Q000031:analogs & derivatives* / Q000276:immunology; D005680:gamma-Aminobutyric Acid / Q000276:immunology
D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; C018361:2-phenyloxazolone; D010081:Oxazolone; D005680:gamma-Aminobutyric Acid