Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires

  1. Yang Yang  Is a corresponding author
  2. Chunlin Wang
  3. Qunying Yang
  4. Aaron B Kantor
  5. Hiutung Chu
  6. Eliver EB Ghosn
  7. Guang Qin
  8. Sarkis K Mazmanian
  9. Jian Han
  10. Leonore A Herzenberg
  1. Stanford University, United States
  2. HudsonAlpha Institute for Biotechnology, United States
  3. California Institute of Technology, United States

Abstract

Processes that define immunoglobulin repertoires are commonly presumed to be the same for all murine B cells. However, studies here that couple high-dimensional FACS sorting with large-scale quantitative IgH deep-sequencing demonstrate that B-1a IgH repertoire differs dramatically from the follicular and marginal zone B cells repertoires and is defined by distinct mechanisms. We track B-1a cells from their early appearance in neonatal spleen to their long-term residence in adult peritoneum and spleen. We show that de novo B-1a IgH rearrangement mainly occurs during the first few weeks of life, after which their repertoire continues to evolve profoundly, including convergent selection of certain V(D)J rearrangements encoding specific CDR3 peptides in all adults and progressive introduction of hypermutation and class-switching as animals age. This V(D)J selection and AID-mediated diversification operate comparably in germ-free and conventional mice, indicating these unique B-1a repertoire-defining mechanisms are driven by antigens that are not derived from microbiota.

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Author details

  1. Yang Yang

    Genetics Department, Stanford University, Stanford, United States
    For correspondence
    yang71@stanford.edu
    Competing interests
    No competing interests declared.
  2. Chunlin Wang

    HudsonAlpha Institute for Biotechnology, Huntsville, United States
    Competing interests
    Chunlin Wang, founder of iRepertoire.
  3. Qunying Yang

    HudsonAlpha Institute for Biotechnology, Huntsville, United States
    Competing interests
    No competing interests declared.
  4. Aaron B Kantor

    Genetics Department, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  5. Hiutung Chu

    Biology and Biological Engineering Department, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  6. Eliver EB Ghosn

    Genetics Department, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  7. Guang Qin

    Genetics Department, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  8. Sarkis K Mazmanian

    Biology and Biological Engineering Department, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  9. Jian Han

    HudsonAlpha Institute for Biotechnology, Huntsville, United States
    Competing interests
    Jian Han, founder of iRepertoire.
  10. Leonore A Herzenberg

    Genetics Department, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.

Copyright

© 2015, Yang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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https://doi.org/10.7554/eLife.09083

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