Role of BCR affinity in T cell dependent antibody responses in vivo.
Antibody affinity for antigen is believed to govern B lymphocyte selection during T-dependent immune responses. To examine antibody affinity in T cell dependent immune responses, we compared mice that carry targeted V(H)B1-8 antibody genes with high or low antigen-binding affinity. We found that high- and low-affinity B cells had the same intrinsic capacity to respond to antigen, but in experiments where limiting numbers of high- and low-affinity B cells were mixed in wild-type recipient mice, only the high-affinity B cells accumulated in germinal centers (GCs). In GCs, high-affinity B cells accumulated fewer V(H) somatic mutations than low affinity B cells. This effect was due to selections as the frequency of mutation in noncoding immunoglobulin gene DNA is the same in high- and low- affinity B cells. Thus, B cells recruited to the GC appeared to undergo a fixed mutation program, regardless of initial B cell receptor affinity. We conclude that in addition to the selection that occurs in GCs, stringent selection for high-affinity clones is also imposed in the early stages of the T cell dependent immune response in vivo.
Shih
Tien-An Yang
TA
Laboratory of Molecular Immunology, The Rockefeller University New York, NY 10021, USA.
Meffre
Eric
E
Roederer
Mario
M
Nussenzweig
Michel C
MC
D000818:Animals; D020296:Animals, Congenic; D000915:Antibody Affinity; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains; D011947:Receptors, Antigen, B-Cell