Research Papers: Immunology:

Novel CXCL13 transgenic mouse: inflammation drives pathogenic effect of CXCL13 in experimental myasthenia gravis

Julia Miriam Weiss, Marieke Robinet, Revital Aricha, Perrine Cufi, Bérengère Villeret, Frida Lantner, Idit Shachar, Sara Fuchs, Miriam C. Souroujon, Sonia Berrih-Aknin and Rozen Le Panse _

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Oncotarget. 2016; 7:7550-7562. https://doi.org/10.18632/oncotarget.6885

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Julia Miriam Weiss1,2,3,4, Marieke Robinet1,2,3,4, Revital Aricha5, Perrine Cufi1,2,3,4, Bérengère Villeret1,2,3,4, Frida Lantner5, Idit Shachar5, Sara Fuchs5, Miriam C. Souroujon6, Sonia Berrih-Aknin1,2,3,4,* and Rozen Le Panse1,2,3,4,*

1 INSERM U974, Paris, France

2 CNRS FRE3617, Paris, France

3 Sorbonne Universités, UPMC University Paris 06, Paris, France

4 AIM, Institut de Myologie, Paris, France

5 Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

6 Open University of Israel, Raanana, Israel

* The authors have contributed equally to this work

Correspondence to:

Rozen Le Panse, email:

Keywords: chemokine, autoimmunity, thymus, B cells, CXCL13-CXCR5, Immunology and Microbiology Section, Immune response, Immunity

Received: September 29, 2015 Accepted: December 23, 2015 Published: January 11, 2016


Abnormal overexpression of CXCL13 is observed in many inflamed tissues and in particular in autoimmune diseases. Myasthenia gravis (MG) is a neuromuscular disease mainly mediated by anti-acetylcholine receptor autoantibodies. Thymic hyperplasia characterized by ectopic germinal centers (GCs) is a common feature in MG and is correlated with high levels of anti-AChR antibodies. We previously showed that the B-cell chemoattractant, CXCL13 is overexpressed by thymic epithelial cells in MG patients. We hypothesized that abnormal CXCL13 expression by the thymic epithelium triggered B-cell recruitment in MG. We therefore created a novel transgenic (Tg) mouse with a keratin 5 driven CXCL13 expression.

The thymus of Tg mice overexpressed CXCL13 but did not trigger B-cell recruitment. However, in inflammatory conditions, induced by Poly(I:C), B cells strongly migrated to the thymus. Tg mice were also more susceptible to experimental autoimmune MG (EAMG) with stronger clinical signs, higher titers of anti-AChR antibodies, increased thymic B cells, and the development of germinal center-like structures. Consequently, this mouse model finally mimics the thymic pathology observed in human MG.

Our data also demonstrated that inflammation is mandatory to reveal CXCL13 ability to recruit B cells and to induce tertiary lymphoid organ development.

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