Early Differentiated CD138highMHCII+IgG+ Plasma Cells Express CXCR3 and Localize into Inflamed Kidneys of Lupus Mice

Abstract

Humoral responses are central to the development of chronic autoimmune diseases such as systemic lupus erythematosus. Indeed, autoantibody deposition is responsible for tissue damage, the kidneys being one of the main target organs. As the source of pathogenic antibodies, plasma cells are therefore critical players in this harmful scenario, both at systemic and local levels. The aim of the present study was to analyze plasma cells in NZB/W lupus mice and to get a better understanding of the mechanisms underlying their involvement in the renal inflammation process. Using various techniques (i.e. flow cytometry, quantitative PCR, ELISpot), we identified and extensively characterized three plasma cell intermediates, according to their B220/CD138/MHCII expression levels. Each of these cell subsets displays specific proliferation and antibody secretion capacities. Moreover, we evidenced that the inflammation-related CXCR3 chemokine receptor is uniquely expressed by CD138highMHCII+ plasma cells, which encompass both short- and long-lived cells and mostly produce IgG (auto)antibodies. Expression of CXCR3 allows efficient chemotactic responsiveness of these cells to cognate chemokines, which production is up-regulated in the kidneys of diseased NZB/W mice. Finally, using fluorescence and electron microscopy, we demonstrated the presence of CD138+CXCR3+IgG+ cells in inflammatory areas in the kidneys, where they are very likely involved in the injury process. Thus, early differentiated CD138highMHCII+ rather than terminally differentiated CD138highMHCIIlow plasma cells may be involved in the renal inflammatory injury in lupus, due to CXCR3 expression and IgG secretion.

Tumor-Infiltrating Plasma Cells Are Associated with Tertiary Lymphoid Structures, Cytolytic T-Cell Responses, and Superior Prognosis in Ovarian Cancer

“…þ PCs have also been described in autoimmunity, where they serve to exacerbate rather than suppress immune responses (38,39). Thus, the immunosuppressive PCs described in prostate cancer (36) may be unique to that disease, as the PCs found in HGSC and other malignancies have properties and associations consistent with a positive role in antitumor immunity.…”

Mesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE

“…Decreases in CD138+ cells may lead to reduced anti-dsDNA antibody production, because CD138 is expressed in B cell precursors and plasma cells that are responsible for autoantibody production2425. It was reported that the levels of circulating soluble CD138, the expression of CD138 mRNA in peripheral mononuclear cells, and the numbers of plasma cells increased in patients with active SLE compared with normal controls26.…”

Myeloid Cells Limit Production of Antibody-Secreting Cells after Immunization in the Lymph Node

“…This difference in mechanism may be due to differences in our vaccination model which lacks the inflammation common to the lupus system. In lupus patients, conditions of chronic inflammation produced by myeloid cells leads to plasmablasts are overrepresented in the blood and in peripheral tissues including kidney (17, 18). It would be interesting to repeat these experiments using strong adjuvants or an infection model where inflammation may change the role that myeloid subsets play regulating ASC responses.…”