TY - JOUR TI - Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching AU - Horns, Felix AU - Vollmers, Christopher AU - Croote, Derek AU - Mackey, Sally F AU - Swan, Gary E AU - Dekker, Cornelia L AU - Davis, Mark M AU - Quake, Stephen R A2 - Neher, Richard A VL - 5 PY - 2016 DA - 2016/08/02 SP - e16578 C1 - eLife 2016;5:e16578 DO - 10.7554/eLife.16578 UR - https://doi.org/10.7554/eLife.16578 AB - 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. KW - antibody KW - class switching KW - repertoire KW - cell decisions JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -