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 VHB1-8 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 VH 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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We thank E. Besmer and members of the Nussenzweig lab for helpful comments on the manuscript and Nai-Ying Zheng for histology. We are also grateful to P. Wilson for help with analysis of somatic hypermutation. Supported by NIH MSTP grant GM07739 (to T. Y. S.) and HHMI and grants from the Leukemia Society and NIH (to M. C. N.).
The authors declare no competing financial interests.
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