A population dynamics model for clonal diversity in a germinal center

Assaf Amitai, Luka Mesin, Gabriel D. Victora, Mehran Kardar, Arup K. Chakraborty

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Germinal centers (GCs) are micro-domains where B cells mature to develop high affinity antibodies. Inside a GC, B cells compete for antigen and T cell help, and the successful ones continue to evolve. New experimental results suggest that, under identical conditions, a wide spectrum of clonal diversity is observed in different GCs, and high affinity B cells are not always the ones selected. We use a birth, death and mutation model to study clonal competition in a GC over time. We find that, like all evolutionary processes, diversity loss is inherently stochastic. We study two selection mechanisms, birth-limited and death limited selection. While death limited selection maintains diversity and allows for slow clonal homogenization as affinity increases, birth limited selection results in more rapid takeover of successful clones. Finally, we qualitatively compare our model to experimental observations of clonal selection in mice.

Original languageEnglish
Article number1693
JournalFrontiers in Microbiology
Volume8
Issue numberSEP
DOIs
StatePublished - 12 Sep 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Amitai, Mesin, Victora, Kardar and Chakraborty.

Funding

Financial support for this work was provided by a grant from the Ragon Institute of MGH, MIT, & Harvard (AC, AA). MK acknowledges support from NSF grant no. DMR-1708280. GV acknowledges support from NIH grant R01 AI119006.

FundersFunder number
National Science Foundation1708280
National Institutes of HealthR01 AI119006
National Sleep FoundationDMR-1708280
Massachusetts General Hospital
Massachusetts Institute of Technology
Ragon Institute of MGH, MIT and Harvard

    Keywords

    • Affinity maturation
    • Clonal evolution
    • Germinal center reaction
    • Modeling and simulations
    • Population dynamics

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