Literature DB >> 26711994

Fluctuating fitness shapes the clone-size distribution of immune repertoires.

Jonathan Desponds1, Thierry Mora2, Aleksandra M Walczak1.   

Abstract

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.

Keywords:  fluctuating fitness; immune repertoire; lymphocyte receptor; population dynamics; repertoire sequencing

Mesh:

Substances:

Year:  2015        PMID: 26711994      PMCID: PMC4720353          DOI: 10.1073/pnas.1512977112

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  39 in total

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8.  Zipf's Law Arises Naturally When There Are Underlying, Unobserved Variables.

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9.  Quantifying size and diversity of the human T cell alloresponse.

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