Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire

Kenta Shinoda; Yaakov Maman; Andres Canela; David G. Schatz; Ferenc Livak; André Nussenzweig

doi:10.1016/j.celrep.2019.11.088

Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire

Kenta Shinoda
, Yaakov Maman
, Andres Canela
, David G. Schatz
, Ferenc Livak
, André Nussenzweig

Bar-Ilan University - Azrieli Faculty of Medicine

National Institutes of Health
Kyoto University
Yale University

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

10 Scopus citations

Abstract

Shinoda et al. demonstrate previously unknown, frequent RAG-dependent recombination within the Ig Vκ gene cluster, which is mediated by evolutionarily conserved flipped RSS embedded in bona fide RSS. These intra-Vκ cluster recombination events alter the available Vκ gene pool by deleting Vκ segments and shape the Vκ-Jκ immune repertoire.

Original language	English
Pages (from-to)	4471-4481.e6
Journal	Cell Reports
Volume	29
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2019.11.088
State	Published - 24 Dec 2019

Bibliographical note

Publisher Copyright:
© 2019 The Author(s)

Funding

We thank Barry P. Sleckman for discussions and the pre-B cells lines; and Frederick W. Alt for suggestions and HTGTS protocols. D.G.S. was supported by NIH grant R01 AI32524 and K.S. was supported by a fellowship from the Uehara Memorial Foundation . Sequencing was performed by NCI CCR Genomics Core and flow cytometry analyses and sorting were performed at the NCI CCR LGI Flow Cytometry Core. The A.N. laboratory is supported by the Intramural Research Program of the NIH ; an Ellison Medical Foundation Senior Scholar in Aging Award ( AG-SS-2633-11 ); the Department of Defense Idea Expansion ( W81XWH-15-2-006 ) and Breakthrough ( W81XWH-16-1-599 ) awards; the Alex Lemonade Stand Foundation Award; and an NIH Intramural FLEX Award. We thank Barry P. Sleckman for discussions and the pre-B cells lines; and Frederick W. Alt for suggestions and HTGTS protocols. D.G.S. was supported by NIH grant R01 AI32524 and K.S. was supported by a fellowship from the Uehara Memorial Foundation. Sequencing was performed by NCI CCR Genomics Core and flow cytometry analyses and sorting were performed at the NCI CCR LGI Flow Cytometry Core. The A.N. laboratory is supported by the Intramural Research Program of the NIH; an Ellison Medical Foundation Senior Scholar in Aging Award (AG-SS-2633-11); the Department of Defense Idea Expansion (W81XWH-15-2-006) and Breakthrough (W81XWH-16-1-599) awards; the Alex Lemonade Stand Foundation Award; and an NIH Intramural FLEX Award. A.N. K.S. Y.M. and F.L. designed experiments. Y.M. performed bioinformatics analyses. K.S. and A.C. performed experiments. F.L. performed fluorescence-activated cell sorting (FACS). D.G.S. and F.L. provided expert advice, and A.N. supervised the project. K.S. Y.M. F.L. and A.N. wrote the manuscript with comments from the other authors. The authors declare no competing interests.

Funders	Funder number
Department of Defense Idea Expansion	W81XWH-15-2-006, W81XWH-16-1-599
National Institutes of Health	R01 AI32524
National Cancer Institute
Ellison Medical Foundation	AG-SS-2633-11
Alex's Lemonade Stand Foundation for Childhood Cancer
Uehara Memorial Foundation

Keywords

END-seq
HTGTS
RAG
VDJ recombination
ig kappa locus
ig repertoire
immunoglobulin
recombination center
recombination signal sequence
variable

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10.1016/j.celrep.2019.11.088

Cite this

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title = "Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire",

abstract = "Shinoda et al. demonstrate previously unknown, frequent RAG-dependent recombination within the Ig Vκ gene cluster, which is mediated by evolutionarily conserved flipped RSS embedded in bona fide RSS. These intra-Vκ cluster recombination events alter the available Vκ gene pool by deleting Vκ segments and shape the Vκ-Jκ immune repertoire.",

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author = "Kenta Shinoda and Yaakov Maman and Andres Canela and Schatz, \{David G.\} and Ferenc Livak and Andr{\'e} Nussenzweig",

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Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire

Abstract

Bibliographical note

Funding

Keywords

Access to Document

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