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Nat Biotechnol. 2017 Sep;35(9):879-884. doi: 10.1038/nbt.3942. Epub 2017 Aug 21.

An atlas of B-cell clonal distribution in the human body.

Author information

1
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
2
School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA.
3
Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
4
LiveOnNY, New York, New York, USA.
5
Department of Surgery and Department of Microbiology and Immunology, Columbia University School of Medicine, New York, New York, USA.
6
Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
7
Department of Microbiology and Immunology, Drexel College of Medicine, Drexel University, Philadelphia, Pennsylvania, USA.

Abstract

B-cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B-cell clones are distributed in the body, we sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments in six human organ donors. We show that large B-cell clones partition into two broad networks-one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B-cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.

PMID:
28829438
PMCID:
PMC5679700
DOI:
10.1038/nbt.3942
[Indexed for MEDLINE]
Free PMC Article

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