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

被引:371
作者
Batista, FD [1 ]
Neuberger, MS [1 ]
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
关键词
D O I
10.1016/S1074-7613(00)80580-4
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:751 / 759
页数:9
相关论文
共 42 条
[1]  
ADORINI L, 1993, J IMMUNOL, V151, P3576
[2]   Acceleration of intracellular targeting of antigen by the B-cell antigen receptor: Importance depends on the nature of the antigen-antibody interaction [J].
Aluvihare, VR ;
Khamlichi, AA ;
Williams, GT ;
Adorini, L ;
Neuberger, MS .
EMBO JOURNAL, 1997, 16 (12) :3553-3562
[3]   3-DIMENSIONAL STRUCTURE OF AN ANTIGEN-ANTIBODY COMPLEX AT 2.8-A RESOLUTION [J].
AMIT, AG ;
MARIUZZA, RA ;
PHILLIPS, SEV ;
POLJAK, RJ .
SCIENCE, 1986, 233 (4765) :747-753
[4]   SMALL REARRANGEMENTS IN STRUCTURES OF FV AND FAB FRAGMENTS OF ANTIBODY D1.3 ON ANTIGEN-BINDING [J].
BHAT, TN ;
BENTLEY, GA ;
FISCHMANN, TO ;
BOULOT, G ;
POLJAK, RJ .
NATURE, 1990, 347 (6292) :483-485
[5]   CD19 - LOWERING THE THRESHOLD FOR ANTIGEN RECEPTOR STIMULATION OF LYMPHOCYTES-B [J].
CARTER, RH ;
FEARON, DT .
SCIENCE, 1992, 256 (5053) :105-107
[6]   COMPARISON OF A STRUCTURAL AND A FUNCTIONAL EPITOPE [J].
CUNNINGHAM, BC ;
WELLS, JA .
JOURNAL OF MOLECULAR BIOLOGY, 1993, 234 (03) :554-563
[7]  
CUNNINGHAM BC, 1993, J MOL BIOL, V237, P513
[8]   PROCESSED ANTIGEN BINDS TO NEWLY SYNTHESIZED MHC CLASS II MOLECULES IN ANTIGEN-SPECIFIC LYMPHOCYTES-B [J].
DAVIDSON, HW ;
REID, PA ;
LANZAVECCHIA, A ;
WATTS, C .
CELL, 1991, 67 (01) :105-116
[9]   VARIATION IN AFFINITIES OF ANTIBODIES DURING IMMUNE RESPONSE [J].
EISEN, HN ;
SISKIND, GW .
BIOCHEMISTRY, 1964, 3 (07) :996-&
[10]   KINETIC MATURATION OF AN IMMUNE-RESPONSE [J].
FOOTE, J ;
MILSTEIN, C .
NATURE, 1991, 352 (6335) :530-532