AUTHOR=Mahévas Matthieu , Michel Marc , Weill Jean-Claude , Reynaud Claude-Agnes TITLE=Long-Lived Plasma Cells in Autoimmunity: Lessons from B-Cell Depleting Therapy JOURNAL=Frontiers in Immunology VOLUME=4 YEAR=2013 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2013.00494 DOI=10.3389/fimmu.2013.00494 ISSN=1664-3224 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.