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Immunity. 2016 Mar 15;44(3):542-552. doi: 10.1016/j.immuni.2016.02.010. Epub 2016 Mar 3.

Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.

Author information

1
Department of Immunology, Duke University, Durham, NC 27710, USA.
2
Laboratory of Molecular Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
3
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
4
Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan.
5
Laboratory of Molecular Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA.
6
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA; Department of Mathematics and Statistics, Boston University, Boston, MA 02118, USA.
7
Department of Immunology, Duke University, Durham, NC 27710, USA; Human Vaccine Institute, Duke University, Durham, NC 27710, USA. Electronic address: ghkelsoe@duke.edu.

Abstract

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.

KEYWORDS:

B cell repertoire; clonal selection; germinal center; influenza hemagglutinin; protective antigen of B. anthracis

PMID:
26948373
PMCID:
PMC4794380
DOI:
10.1016/j.immuni.2016.02.010
[Indexed for MEDLINE]
Free PMC Article

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