B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes

Joel N. H. Stern; Gur Yaari; Jason A. Vander Heiden; George Church; William F. Donahue; Rogier Q. Hintzen; Anita J. Huttner; Jon D. Laman; Rashed M. Nagra; Alyssa Nylander; David Pitt; Sriram Ramanan; Bilal A. Siddiqui; Francois Vigneault; Steven H. Kleinstein; David A. Hafler; Kevin C. O’Connor

doi:10.1126/scitranslmed.3008879

Research ArticleMultiple Sclerosis

B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes

Joel N. H. Stern¹,*,†,
Gur Yaari²,³,*,
Jason A. Vander Heiden⁴,*,
George Church⁵,
William F. Donahue⁶,
Rogier Q. Hintzen⁷,
Anita J. Huttner²,
Jon D. Laman⁸,
Rashed M. Nagra⁹,
Alyssa Nylander¹,
David Pitt¹,
Sriram Ramanan¹,
Bilal A. Siddiqui¹,
Francois Vigneault⁵,⁶,
Steven H. Kleinstein²,⁴,‡§,
David A. Hafler¹,¹⁰,‡§ and
Kevin C. O’Connor¹,‡§

¹Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA.
²Department of Pathology, Yale School of Medicine, New Haven, CT 06511, USA.
³Bioengineering Program, Faculty of Engineering, Bar-Ilan University, Ramat Gan 52900, Israel.
⁴Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.
⁵Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
⁶AbVitro Incorporated, Boston, MA 02210, USA.
⁷Department of Neurology, Erasmus MC, University Medical Center Rotterdam, and MS Centrum ErasMS, 3000 CA Rotterdam, the Netherlands.
⁸Department of Immunology, Erasmus MC, University Medical Center Rotterdam, and MS Centrum ErasMS, 3000 CA Rotterdam, the Netherlands.
⁹Neurology Research, West Los Angeles VA Medical Center, Los Angeles, CA 90073, USA.
¹⁰Department of Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.

↵§Corresponding author. E-mail: steven.kleinstein{at}yale.edu (S.H.K.); david.hafler{at}yale.edu (D.A.H.); kevin.oconnor{at}yale.edu (K.C.O.)

↵* These authors equally contributed to this work.
↵† Present address: Department of Science Education, Hofstra North Shore-LIJ School of Medicine, Hofstra University, Hempstead, NY 11530, USA.
↵‡ Co-senior authors.

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Science Translational Medicine 06 Aug 2014:
Vol. 6, Issue 248, pp. 248ra107
DOI: 10.1126/scitranslmed.3008879

Joel N. H. Stern

1Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA.

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Gur Yaari

2Department of Pathology, Yale School of Medicine, New Haven, CT 06511, USA.

3Bioengineering Program, Faculty of Engineering, Bar-Ilan University, Ramat Gan 52900, Israel.

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Jason A. Vander Heiden

4Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.

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George Church

5Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

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William F. Donahue

6AbVitro Incorporated, Boston, MA 02210, USA.

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Rogier Q. Hintzen

7Department of Neurology, Erasmus MC, University Medical Center Rotterdam, and MS Centrum ErasMS, 3000 CA Rotterdam, the Netherlands.

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Anita J. Huttner

2Department of Pathology, Yale School of Medicine, New Haven, CT 06511, USA.

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Jon D. Laman

8Department of Immunology, Erasmus MC, University Medical Center Rotterdam, and MS Centrum ErasMS, 3000 CA Rotterdam, the Netherlands.

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Rashed M. Nagra

9Neurology Research, West Los Angeles VA Medical Center, Los Angeles, CA 90073, USA.

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Alyssa Nylander

1Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA.

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David Pitt

1Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA.

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Sriram Ramanan

1Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA.

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Bilal A. Siddiqui

1Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA.

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Francois Vigneault

5Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

6AbVitro Incorporated, Boston, MA 02210, USA.

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Steven H. Kleinstein

2Department of Pathology, Yale School of Medicine, New Haven, CT 06511, USA.

4Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.

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For correspondence: steven.kleinstein@yale.edu david.hafler@yale.edu kevin.oconnor@yale.edu

David A. Hafler

1Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA.

10Department of Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.

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For correspondence: steven.kleinstein@yale.edu david.hafler@yale.edu kevin.oconnor@yale.edu

Kevin C. O’Connor

1Department of Neurology, Yale School of Medicine, New Haven, CT 06511, USA.

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For correspondence: steven.kleinstein@yale.edu david.hafler@yale.edu kevin.oconnor@yale.edu

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B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes

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