Fluctuating fitness shapes the clone size distribution of immune repertoires

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 regards 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.

References in corpus (4)

• Power-law distributions in empirical data
• Statistical inference of the generation probability of T-cell receptors from sequence repertoires
• The Impact of Environmental Fluctuations on Evolutionary Fitness Functions
• Assessing T cell clonal size distribution: a non-parametric approach

Cited by in corpus (24)

• Multiple-scale stochastic processes: decimation, averaging and beyond
• How many different clonotypes do immune repertoires contain?
• Quantitative Immunology for Physicists
• Resist or perish: fate of a microbial population subjected to a periodic presence of antimicrobial
• Early life imprints the hierarchy of T cell clone sizes
• Tuning environmental timescales to evolve and maintain generalists
• Hierarchy and extremes in selections from pools of randomized proteins
• Rényi entropy, abundance distribution and the equivalence of ensembles
• Quantifying the impact of a periodic presence of antimicrobial on resistance evolution in a homogeneous microbial population of fixed size
• Immune Fingerprinting through Repertoire Similarity
• Exact steady-state distributions of multispecies birth-death-immigration processes: effects of mutations and carrying capacity on diversity
• How adaptive immunity constrains the composition and fate of large bacterial populations
• Population Extinction on a Random Fitness Seascape
• Immigration-induced phase transition in a regulated multispecies birth-death process
• The role of idiotypic interactions in the adaptive immune system: a belief-propagation approach
• A Seascape Origin of Richards Growth
• Understanding how T helper cells learn to coordinate effective immune responses through the lens of reinforcement learning
• The role of T-helper/T-suppressor ratio in the adaptive immune response: a dynamical model
• Affinity maturation for an optimal balance between long-term immune coverage and short-term resource constraints
• Better lower bounds for missing species: improved non-parametric moment-based estimation for large experiments
• Statistical mechanics of clonal expansion in lymphocyte networks modelled with slow and fast variables
• Complex physical properties of an adaptive, self-organizing biological system
• How heterogeneous thymic output and homeostatic proliferation shape naive T cell receptor clone abundance distributions
• A mathematical model of the effects of aging on naive T-cell population and diversity