title: Long-lived plasma cells in autoimmunity: lessons from B-cell depleting therapy.
abstract: A large number of auto-immune diseases are treated with rituximab, an antibody against CD20 that depletes most of the B-cells in the organism. The response to this treatment depends largely on the disease and the type of lymphoid cells involved in the auto-immune process. We recently reported that B-cell depletion in immune thrombocytopenia induced the appearance of pathogenic long-lived plasma cells in the spleen, which were not present before treatment or in non-auto-immune conditions. The spleen of treated patients produced an excess of the cytokine B-cell activating factor, which in in vitro-cultured splenic cells, could increase the longevity of plasma cells. Our results suggested that, paradoxically, the B-cell depletion itself, by altering the splenic milieu, promoted the differentiation of short-lived auto-immune plasma cells into long-lived ones. We describe the cellular and cytokinic components of the splenic plasma cell niche, notably CD4(+) T cells and discuss possible survival factors that could be targeted simultaneously with rituximab-mediated B-cell depletion to interfere with plasma cell persistence.
authors.affiliation: INSERM UMR783, Faculté de Médecine-Site Broussais, Université Paris Descartes , Paris , France ; INSERM U955, Établissement français du sang (EFS) Île-de-France, Hôpital Henri-Mondor , Créteil , France ; Service de Médecine Interne, Centre de référence des cytopénies auto-immunes de l'adulte, Hôpital Henri-Mondor, Assistance Publique Hôpitaux de Paris, Université Paris-Est Créteil , Créteil , France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Mahévas
authors.affiliation: Service de Médecine Interne, Centre de référence des cytopénies auto-immunes de l'adulte, Hôpital Henri-Mondor, Assistance Publique Hôpitaux de Paris, Université Paris-Est Créteil , Créteil , France.
authors.forename: Marc
authors.initials: M
authors.lastname: Michel
authors.affiliation: INSERM UMR783, Faculté de Médecine-Site Broussais, Université Paris Descartes , Paris , France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Weill
authors.affiliation: INSERM UMR783, Faculté de Médecine-Site Broussais, Université Paris Descartes , Paris , France.
authors.forename: Claude-Agnès
authors.initials: CA
authors.lastname: Reynaud
keywords: BAFF/Blys; autoreactive antibody; belimumab; plasma cell niche; rituximab