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Front Immunol. 2013 Dec 27;4:494. doi: 10.3389/fimmu.2013.00494.

Long-lived plasma cells in autoimmunity: lessons from B-cell depleting therapy.

Author information

1
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.
2
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.
3
INSERM UMR783, Faculté de Médecine-Site Broussais, Université Paris Descartes , Paris , France.

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.

KEYWORDS:

BAFF/Blys; autoreactive antibody; belimumab; plasma cell niche; rituximab

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