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

Jonathan Desponds, Thierry Mora, Aleksandra M Walczak

Proceedings of the National Academy of Sciences of the United States of America 2016 Jan 12

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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.

Citation

Jonathan Desponds, Thierry Mora, Aleksandra M Walczak. Fluctuating fitness shapes the clone-size distribution of immune repertoires. Proceedings of the National Academy of Sciences of the United States of America. 2016 Jan 12;113(2):274-9