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Related Concept Videos

T Cell Activation and Clonal Selection01:22

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Mutation, Gene Flow, and Genetic Drift01:09

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In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
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Diploid organisms have two alleles of each gene, one from each parent, in their somatic cells. Therefore, each individual contributes two alleles to the gene pool of the population. The gene pool of a population is the sum of every allele of all genes within that population and has some degree of variation. Genetic variation is typically expressed as a relative frequency, which is the percentage of the total population that has a given allele, genotype or phenotype.
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Related Experiment Video

Updated: Sep 15, 2025

Interrogating Individual Autoreactive Germinal Centers by Photoactivation in a Mixed Chimeric Model of Autoimmunity
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Replaying germinal center evolution on a quantified affinity landscape.

William S DeWitt1,2, Ashni A Vora3, Tatsuya Araki3,4

  • 1Department of Genome Sciences, University of Washington, Seattle, WA, USA.

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|July 15, 2025
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Summary
This summary is machine-generated.

Germinal center (GC) B cell evolution shapes antibody affinity through cumulative selection and somatic hypermutation (SHM) biases. Survivorship biases distort our understanding of GC evolutionary dynamics and affinity progression over time.

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Area of Science:

  • Immunology
  • Evolutionary Biology
  • Molecular Biology

Background:

  • Antibody affinity maturation in germinal centers (GCs) is crucial for adaptive immunity.
  • The evolutionary dynamics governing this process, particularly the role of competition and selection, are not fully understood.

Purpose of the Study:

  • To characterize the dynamical evolutionary features of antibody affinity maturation within GCs.
  • To investigate how selection and somatic hypermutation (SHM) shape GC B cell evolution.
  • To understand the impact of survivorship biases on perceived affinity progression.

Main Methods:

  • Developed an experimental evolution model to repeatedly simulate GC reactions.
  • Utilized deep mutational scanning to assign affinities to individual B cells.
  • Employed time-calibrated models to analyze evolutionary trajectories.

Main Results:

  • GCs achieve predictable evolutionary outcomes through cumulative imperfect selection.
  • Somatic hypermutation (SHM) targeting biases significantly shape the evolutionary landscape.
  • Survivorship biases distort the apparent progression of antibody affinity over time, explaining phenomena like permissiveness to low-affinity lineages and early plateauing.

Conclusions:

  • The evolutionary trajectory of antibody affinity in GCs is a result of cumulative selection acting on a landscape influenced by SHM biases.
  • Apparent features of GC evolution are significantly shaped by survivorship biases, necessitating careful interpretation of affinity progression data.