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Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.

Publication ,  Journal Article
Kuraoka, M; Schmidt, AG; Nojima, T; Feng, F; Watanabe, A; Kitamura, D; Harrison, SC; Kepler, TB; Kelsoe, G
Published in: Immunity
March 15, 2016

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.

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

March 15, 2016

Volume

44

Issue

3

Start / End Page

542 / 552

Location

United States

Related Subject Headings

  • Single-Domain Antibodies
  • Receptors, Antigen, B-Cell
  • Orthomyxoviridae
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Immunology
  • Immunity, Humoral
  • Humans
  • Hemagglutinins, Viral
 

Citation

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Kuraoka, M., Schmidt, A. G., Nojima, T., Feng, F., Watanabe, A., Kitamura, D., … Kelsoe, G. (2016). Complex Antigens Drive Permissive Clonal Selection in Germinal Centers. Immunity, 44(3), 542–552. https://doi.org/10.1016/j.immuni.2016.02.010
Kuraoka, Masayuki, Aaron G. Schmidt, Takuya Nojima, Feng Feng, Akiko Watanabe, Daisuke Kitamura, Stephen C. Harrison, Thomas B. Kepler, and Garnett Kelsoe. “Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.Immunity 44, no. 3 (March 15, 2016): 542–52. https://doi.org/10.1016/j.immuni.2016.02.010.
Kuraoka M, Schmidt AG, Nojima T, Feng F, Watanabe A, Kitamura D, et al. Complex Antigens Drive Permissive Clonal Selection in Germinal Centers. Immunity. 2016 Mar 15;44(3):542–52.
Kuraoka, Masayuki, et al. “Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.Immunity, vol. 44, no. 3, Mar. 2016, pp. 542–52. Pubmed, doi:10.1016/j.immuni.2016.02.010.
Kuraoka M, Schmidt AG, Nojima T, Feng F, Watanabe A, Kitamura D, Harrison SC, Kepler TB, Kelsoe G. Complex Antigens Drive Permissive Clonal Selection in Germinal Centers. Immunity. 2016 Mar 15;44(3):542–552.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

March 15, 2016

Volume

44

Issue

3

Start / End Page

542 / 552

Location

United States

Related Subject Headings

  • Single-Domain Antibodies
  • Receptors, Antigen, B-Cell
  • Orthomyxoviridae
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Immunology
  • Immunity, Humoral
  • Humans
  • Hemagglutinins, Viral