title: Novel CXCL13 transgenic mouse: inflammation drives pathogenic effect of CXCL13 in experimental myasthenia gravis.
abstract: 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.
authors.affiliation: INSERM U974, Paris, France.|CNRS FRE3617, Paris, France.|Sorbonne Universités, UPMC University Paris 06, Paris, France.|AIM, Institut de Myologie, Paris, France.
authors.forename: Julia Miriam
authors.initials: JM
authors.lastname: Weiss
authors.affiliation: INSERM U974, Paris, France.|CNRS FRE3617, Paris, France.|Sorbonne Universités, UPMC University Paris 06, Paris, France.|AIM, Institut de Myologie, Paris, France.
authors.forename: Marieke
authors.initials: M
authors.lastname: Robinet
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Revital
authors.initials: R
authors.lastname: Aricha
authors.affiliation: INSERM U974, Paris, France.|CNRS FRE3617, Paris, France.|Sorbonne Universités, UPMC University Paris 06, Paris, France.|AIM, Institut de Myologie, Paris, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Cufi
authors.affiliation: INSERM U974, Paris, France.|CNRS FRE3617, Paris, France.|Sorbonne Universités, UPMC University Paris 06, Paris, France.|AIM, Institut de Myologie, Paris, France.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Villeret
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Frida
authors.initials: F
authors.lastname: Lantner
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Idit
authors.initials: I
authors.lastname: Shachar
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Open University of Israel, Raanana, Israel.
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Souroujon
authors.affiliation: INSERM U974, Paris, France.|CNRS FRE3617, Paris, France.|Sorbonne Universités, UPMC University Paris 06, Paris, France.|AIM, Institut de Myologie, Paris, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Berrih-Aknin
authors.affiliation: INSERM U974, Paris, France.|CNRS FRE3617, Paris, France.|Sorbonne Universités, UPMC University Paris 06, Paris, France.|AIM, Institut de Myologie, Paris, France.
authors.forename: Rozen
authors.initials: R
authors.lastname: Le Panse
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013952:Thymus Hyperplasia / Q000503:physiopathology*
chemical_list: D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; D012333:RNA, Messenger
keywords: B cells; CXCL13-CXCR5; Immune response; Immunity; Immunology and Microbiology Section; autoimmunity; chemokine; thymus