Fluctuating fitness shapes the clone-size distribution of immune repertoires

The adaptive immune system relies on the diversity of receptors expressed on the surface of B- and T cells to protect the organism from a vast amount of pathogenic threats. The proliferation and degradation dynamics of different cell types (B cells, T cells, naive, memory) is governed by a variety o...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2016-01, Vol.113 (2), p.274-279
Main Authors: Desponds, Jonathan, Mora, Thierry, Walczak, Aleksandra M.
Format: Article
Language:English
Subjects:
Adaptive Immunity
Antigens - immunology
Biological Sciences
Cell Size
Cellular biology
Clonal Evolution
Clone Cells
Cloning
Evolutionary biology
Gene expression
Immunology
Models, Immunological
Phenotype
Physical Sciences
Signal transduction
T cell receptors
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Summary:The adaptive immune system relies on the diversity of receptors expressed on the surface of B- and T cells to protect the organism from a vast amount of pathogenic threats. The proliferation and degradation dynamics of different cell types (B cells, T cells, naive, memory) is governed by a variety of antigenic and environmental signals, yet the observed clone sizes follow a universal power-law distribution. Guided by this reproducibility we propose effective models of somatic evolution where cell fate depends on an effective fitness. This fitness is determined by growth factors acting either on clones of cells with the same receptor responding to specific antigens, or directly on single cells with no regard for clones. We identify fluctuations in the fitness acting specifically on clones as the essential ingredient leading to the observed distributions. Combining our models with experiments, we characterize the scale of fluctuations in antigenic environments and we provide tools to identify the relevant growth signals in different tissues and organisms. Our results generalize to any evolving population in a fluctuating environment.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1512977112