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.
|Number of pages||8|
|State||Published - 1 Sep 2017|
Bibliographical noteFunding 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.
© 2017 Nature America, Inc.
ASJC Scopus subject areas
- Applied Microbiology and Biotechnology
- Molecular Medicine
- Biomedical Engineering