Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Adoptive Transfer of Long-Lived Plasma Cells from NZB/W Mice Causes Immune Complex Nephritis in Recipient Rag1/ Mice.
Cheng3, Quingyu, Mumtaz1, Imtiaz M., Hoyer1, Bimba F., Radbruch4, Andreas, Hiepe2, Falk
Charité - Universitätsmedizin, Berlin, Germany
Charité - Universitätsmedizin, Berlin, Berlin, Germany
Charité - Universitätsmedizin Berlin, Berlin, Germany
German Rheumatism Research Center, Berlin, Germany
Previously, we showed that long-lived plasma cells refractory to immunosuppression significantly contribute to autoantibody production in NZB/W mice used as a model of lupus nephritis. Since immunosuppressive and B cell depletion therapy affecting only short-lived plasmablasts and plasma cells can induce remission of the disease, the role of surviving long-lived plasma cells in the pathogenesis of the disease is not well-defined.
To elucidate the role of autoreactive long-lived plasma cells in the pathogenesis of lupus nephritis.
CD138+ plasmablasts and plasma cells were isolated by MACS technology from the spleens of >6-month-old NZB/W mice with high levels of anti-dsDNA antibodies and adoptively transferred to immunodeficient Rag1-/- mice (3 million cells/mouse). Contamination with B cells was about 2% and with T cells 0.02%. To exclude a contribution of these contaminated B cells, the corresponding number of B cells was transferred in a control experiment. Serum antibody levels in recipient mice were measured using ELISA. The recipient mice were sacrificed 21 weeks after adoptive transfer for analysis of plasma cells, including anti-DNA-secreting cells, by flow cytometry and ELISPOT as well as for renal immunohistology.
Total IgG, total IgM and IgG and IgM anti-dsDNA antibody levels were measured in recipient mice starting one week after transfer and remained constant for the entire observation (21 weeks), even after cyclophosphamide treatment. Mature non-dividing plasma cells but not plasmablasts were detected in bone marrow, spleen, and kidneys of the recipient mice. Adoptive transfer of B cells in numbers corresponding to the B-cell contamination levels within the transferred plasmablast fraction did not result in significant antibody (autoantibody) levels. Proteinuria developed 21 weeks after plasma cell transfer. Renal immunohistology showed immune complex nephritis with deposition of IgG, IgM and C3.
Adoptive transfer of plasmablasts results in homing of long-lived plasma cells in spleen and bone barrow. Autoantibodies secreted by long-lived plasma cells can cause nephritis. This supports the suggestion to consider long-lived plasma cells refractory to conventional immunosuppression and B cell depletion as candidate targets for future therapeutic strategies.
To cite this abstract, please use the following information:
Cheng, Quingyu, Mumtaz, Imtiaz M., Hoyer, Bimba F., Radbruch, Andreas, Hiepe, Falk; Adoptive Transfer of Long-Lived Plasma Cells from NZB/W Mice Causes Immune Complex Nephritis in Recipient Rag1/ Mice. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1414