title: Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires.
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.
authors.affiliation: Genetics Department, Stanford University, Stanford, United States.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, United States.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Wang
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, United States.
authors.forename: Qunying
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Genetics Department, Stanford University, Stanford, United States.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Kantor
authors.affiliation: Biology and Biological Engineering Department, California Institute of Technology, Pasadena, United States.
authors.forename: Hiutung
authors.initials: H
authors.lastname: Chu
authors.affiliation: Genetics Department, Stanford University, Stanford, United States.
authors.forename: Eliver Eb
authors.initials: EE
authors.lastname: Ghosn
authors.affiliation: Genetics Department, Stanford University, Stanford, United States.
authors.forename: Guang
authors.initials: G
authors.lastname: Qin
authors.affiliation: Biology and Biological Engineering Department, California Institute of Technology, Pasadena, United States.
authors.forename: Sarkis K
authors.initials: SK
authors.lastname: Mazmanian
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, United States.
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.affiliation: Genetics Department, Stanford University, Stanford, United States.
authors.forename: Leonore A
authors.initials: LA
authors.lastname: Herzenberg
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015322:Gene Rearrangement, B-Lymphocyte; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D010537:Peritoneum / Q000276:immunology; D013154:Spleen / Q000276:immunology
chemical_list: D007143:Immunoglobulin Heavy Chains
keywords: IgH; V(D)J; cell biology; diversify; immunology; mouse