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

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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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Yang Yang

Genetics Department, Stanford University, Stanford, United States

For correspondence
yang71@stanford.edu

Competing interests
No competing interests declared.
Chunlin Wang

HudsonAlpha Institute for Biotechnology, Huntsville, United States

Competing interests
Chunlin Wang, founder of iRepertoire.
Qunying Yang

HudsonAlpha Institute for Biotechnology, Huntsville, United States

Competing interests
No competing interests declared.
Aaron B Kantor

Genetics Department, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Hiutung Chu

Biology and Biological Engineering Department, California Institute of Technology, Pasadena, United States

Competing interests
No competing interests declared.
Eliver EB Ghosn

Genetics Department, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Guang Qin

Genetics Department, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Sarkis K Mazmanian

Biology and Biological Engineering Department, California Institute of Technology, Pasadena, United States

Competing interests
No competing interests declared.
Jian Han

HudsonAlpha Institute for Biotechnology, Huntsville, United States

Competing interests
Jian Han, founder of iRepertoire.
Leonore A Herzenberg

Genetics Department, Stanford University, Stanford, United States

Competing interests
No competing interests declared.

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