title: Interferon-α induces unabated production of short-lived plasma cells in pre-autoimmune lupus-prone (NZB×NZW)F1 mice but not in BALB/c mice.
abstract: IFN-α is known to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanisms remain unclear. We previously showed that within weeks, exposure to IFN-α in vivo induces lupus in pre-autoimmune lupus-prone NZB×NZW F1 (NZB/W) but not in BALB/c mice. In the current study, we show that in vivo expression of IFN-α induces sustained B-cell proliferation in both BALB/c and NZB/W mice. In NZB/W but not BALB/c mice, B-cell proliferation was accompanied by a rapid and unabated production of autoantibody-secreting cells (ASCs) in secondary lymphoid organs, suggesting that a B-cell checkpoint is altered in the autoimmune background. The majority (>95%) of ASCs elicited in IFN-α-treated NZB/W mice were short-lived and occurred without the induction of long-lived plasma cells. A short course of cyclophosphamide caused a sharp drop in IFN-α-elicited short-lived plasma cells, but the levels recovered within days following termination of treatment. Thus, our work provides new insights into effectiveness and limitations of the current SLE therapies.
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.forename: Mike
authors.initials: M
authors.lastname: Gallegos
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Sophie
authors.initials: S
authors.lastname: Koutouzov
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010950:Plasma Cells / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins; D013045:Species Specificity
chemical_list: D007166:Immunosuppressive Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D003520:Cyclophosphamide