title: Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching.
abstract: Antibody class switching is a feature of the adaptive immune system which enables diversification of the effector properties of antibodies. Even though class switching is essential for mounting a protective response to pathogens, the in vivo patterns and lineage characteristics of antibody class switching have remained uncharacterized in living humans. Here we comprehensively measured the landscape of antibody class switching in human adult twins using antibody repertoire sequencing. The map identifies how antibodies of every class are created and delineates a two-tiered hierarchy of class switch pathways. Using somatic hypermutations as a molecular clock, we discovered that closely related B cells often switch to the same class, but lose coherence as somatic mutations accumulate. Such correlations between closely related cells exist when purified B cells class switch in vitro, suggesting that class switch recombination is directed toward specific isotypes by a cell-autonomous imprinted state.
authors.affiliation: Biophysics Graduate Program, Stanford University, Stanford, United States.
authors.forename: Felix
authors.identifier: 0000-0001-5872-5061
authors.initials: F
authors.lastname: Horns
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, United States.|Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Vollmers
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, United States.
authors.forename: Derek
authors.identifier: 0000-0003-4907-1865
authors.initials: D
authors.lastname: Croote
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, United States.
authors.forename: Sally F
authors.initials: SF
authors.lastname: Mackey
authors.affiliation: Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, United States.|Department of Medicine, Stanford University School of Medicine, Stanford, United States.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Swan
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, United States.
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States.|Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, United States.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, United States.|Department of Applied Physics, Stanford University, Stanford, United States.|Howard Hughes Medical Institute, Chevy Chase, United States.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Quake
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D007155:Immunologic Factors / Q000235:genetics*; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D007132:Immunoglobulin Isotypes; D007155:Immunologic Factors
keywords: antibody; cell decisions; class switching; computational biology; human; immunology; repertoire; systems biology