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

Wenzhao Meng; Bochao Zhang; Gregory W. Schwartz; Aaron M. Rosenfeld; Daqiu Ren; Joseph J.C. Thome; Dustin J. Carpenter; Nobuhide Matsuoka; Harvey Lerner; Amy L. Friedman; Tomer Granot; Donna L. Farber; Mark J. Shlomchik; Uri Hershberg; Eline T. Luning Prak

doi:10.1038/nbt.3942

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

Wenzhao Meng, Bochao Zhang, Gregory W. Schwartz, Aaron M. Rosenfeld, Daqiu Ren, Joseph J.C. Thome, Dustin J. Carpenter, Nobuhide Matsuoka, Harvey Lerner, Amy L. Friedman, Tomer Granot, Donna L. Farber, Mark J. Shlomchik, Uri Hershberg, Eline T. Luning Prak

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	879-886
Number of pages	8
Journal	Nature Biotechnology
Volume	35
Issue number	9
DOIs	https://doi.org/10.1038/nbt.3942
State	Published - 1 Sep 2017
Externally published	Yes

Bibliographical note

Funding Information:
We thank the Human Immunology Core facility at the University of Pennsylvania for assistance with cell preparations and sequencing support. We thank Y. Louzoun, M. Cancro and R. Thomas Jr. for discussions. We thank the organ donor families and the LiveOnNY transplant staff and coordinators. This work was supported by NIH P01 AI106697 (D.L.F., U.H., M.J.S., W.M., B.Z., A.M.R., D.R., D.J.C., N.M., T.G. and E.T.L.P.), P30-CA016520 (E.T.L.P.) and F31AG047003 (J.J.C.T.). G.W.S. was funded by the US Department of Education Graduate Assistance in Areas of National Need (GAANN) program, CFDA Number: 84.200.

Publisher Copyright:
© 2017 Nature America, Inc.

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nbt.3942

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title = "An atlas of B-cell clonal distribution in the human body",

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.",

author = "Wenzhao Meng and Bochao Zhang and Schwartz, {Gregory W.} and Rosenfeld, {Aaron M.} and Daqiu Ren and Thome, {Joseph J.C.} and Carpenter, {Dustin J.} and Nobuhide Matsuoka and Harvey Lerner and Friedman, {Amy L.} and Tomer Granot and Farber, {Donna L.} and Shlomchik, {Mark J.} and Uri Hershberg and {Luning Prak}, {Eline T.}",

note = "Funding Information: We thank the Human Immunology Core facility at the University of Pennsylvania for assistance with cell preparations and sequencing support. We thank Y. Louzoun, M. Cancro and R. Thomas Jr. for discussions. We thank the organ donor families and the LiveOnNY transplant staff and coordinators. This work was supported by NIH P01 AI106697 (D.L.F., U.H., M.J.S., W.M., B.Z., A.M.R., D.R., D.J.C., N.M., T.G. and E.T.L.P.), P30-CA016520 (E.T.L.P.) and F31AG047003 (J.J.C.T.). G.W.S. was funded by the US Department of Education Graduate Assistance in Areas of National Need (GAANN) program, CFDA Number: 84.200. Publisher Copyright: {\textcopyright} 2017 Nature America, Inc.",

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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