Role of BCR affinity in T cell dependent antibody responses in vivo

Nat Immunol. 2002 Jun;3(6):570-5. doi: 10.1038/ni803. Epub 2002 May 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Congenic
  • Antibody Affinity
  • Antibody Formation*
  • B-Lymphocytes / immunology
  • Cell Differentiation
  • Female
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Immunoglobulin Heavy Chains / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation
  • Receptors, Antigen, B-Cell / metabolism*
  • T-Lymphocytes / immunology*


  • Immunoglobulin Heavy Chains
  • Receptors, Antigen, B-Cell