AIRR-C Seminar Series, April 27, 2023 - Marcos Vieria, University of Chicago, USA
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Germline-encoded specificities and the predictability
Germline-encoded specificities and the predictability of the B cell response in models and experiments
Early Career Speaker: Marcos Vieria, University of Chicago, USA
Abstract:
Antibodies result from the competition of B cell lineages evolving under selection for improved antigen recognition, a process known as affinity maturation. High-affinity antibodies to pathogens such as HIV, influenza, and SARS-CoV-2 are frequently reported to arise from B cells whose receptors are encoded by particular immunoglobulin genes. This raises the possibility that the presence of particular germline genes in the B cell repertoire is a major determinant of the quality of the antibody response. Alternatively, initial differences in germline genes’ propensities to form high-affinity receptors might be overcome by chance events during affinity maturation. We first show how this can happen in simulations: even when fitness differences between germline genes lead to similar gene usage across individuals early on, gene usage can become increasingly dissimilar over time. We next find that mice experimentally infected with influenza virus demonstrate the same pattern of divergence in the weeks following infection. We investigated whether affinity maturation might nonetheless strongly select for particular amino acid motifs across diverse genetic backgrounds, but we found no evidence of convergence to similar CDR3 sequences or amino acid substitutions. These results suggest germline-encoded specificities might enable fast recognition of specific antigens early in the response, but diverse evolutionary routes to high affinity limit the genetic predictability of responses to infection and vaccination in the long term.
Speaker Bio:
Marcos Vieira is a Senior Research Scientist in the Cobey Lab at the University of Chicago, where he also obtained his PhD. He uses computational, statistical and mathematical tools to study immunity at different scales, from the within-host evolution of B cells to the effects of host immune history on the epidemiology and evolution of viruses.
AIRR-C Seminar Series website: https://www.antibodysociety.org/the-a...
Early Career Speaker: Marcos Vieria, University of Chicago, USA
Abstract:
Antibodies result from the competition of B cell lineages evolving under selection for improved antigen recognition, a process known as affinity maturation. High-affinity antibodies to pathogens such as HIV, influenza, and SARS-CoV-2 are frequently reported to arise from B cells whose receptors are encoded by particular immunoglobulin genes. This raises the possibility that the presence of particular germline genes in the B cell repertoire is a major determinant of the quality of the antibody response. Alternatively, initial differences in germline genes’ propensities to form high-affinity receptors might be overcome by chance events during affinity maturation. We first show how this can happen in simulations: even when fitness differences between germline genes lead to similar gene usage across individuals early on, gene usage can become increasingly dissimilar over time. We next find that mice experimentally infected with influenza virus demonstrate the same pattern of divergence in the weeks following infection. We investigated whether affinity maturation might nonetheless strongly select for particular amino acid motifs across diverse genetic backgrounds, but we found no evidence of convergence to similar CDR3 sequences or amino acid substitutions. These results suggest germline-encoded specificities might enable fast recognition of specific antigens early in the response, but diverse evolutionary routes to high affinity limit the genetic predictability of responses to infection and vaccination in the long term.
Speaker Bio:
Marcos Vieira is a Senior Research Scientist in the Cobey Lab at the University of Chicago, where he also obtained his PhD. He uses computational, statistical and mathematical tools to study immunity at different scales, from the within-host evolution of B cells to the effects of host immune history on the epidemiology and evolution of viruses.
AIRR-C Seminar Series website: https://www.antibodysociety.org/the-a...
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