Journal
NATURE IMMUNOLOGY
Volume 3, Issue 6, Pages 570-575Publisher
NATURE AMERICA INC
DOI: 10.1038/ni803
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- NIGMS NIH HHS [GM07739] Funding Source: Medline
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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.
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