Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.

Published

Journal Article

Germinal center (GC) B cells evolve toward increased affinity by a Darwinian process that has been studied primarily in genetically restricted, hapten-specific responses. We explored the population dynamics of genetically diverse GC responses to two complex antigens-Bacillus anthracis protective antigen and influenza hemagglutinin-in which B cells competed both intra- and interclonally for distinct epitopes. Preferred VH rearrangements among antigen-binding, naive B cells were similarly abundant in early GCs but, unlike responses to haptens, clonal diversity increased in GC B cells as early "winners" were replaced by rarer, high-affinity clones. Despite affinity maturation, inter- and intraclonal avidities varied greatly, and half of GC B cells did not bind the immunogen but nonetheless exhibited biased VH use, V(D)J mutation, and clonal expansion comparable to antigen-binding cells. GC reactions to complex antigens permit a range of specificities and affinities, with potential advantages for broad protection.

Full Text

Duke Authors

Cited Authors

  • Kuraoka, M; Schmidt, AG; Nojima, T; Feng, F; Watanabe, A; Kitamura, D; Harrison, SC; Kepler, TB; Kelsoe, G

Published Date

  • March 15, 2016

Published In

Volume / Issue

  • 44 / 3

Start / End Page

  • 542 - 552

PubMed ID

  • 26948373

Pubmed Central ID

  • 26948373

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2016.02.010

Language

  • eng

Conference Location

  • United States