Systemic activation of B and CD4 but not CD8 cells drives early disease in lupus prone mice, while macrophages, CD4 and CD8 cells infiltrate the kidney with the exclusion of B cells

• Published in: The Journal of immunology (1950) 2019-05, Vol.202 (1_Supplement), p.179-179.1
• Main Authors: Wu, Juan, Wang, Hongsheng, Amo, Laura, Scott, Bethany, Kole, Hemanta K, Bolland, Silvia
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.202.Supp.179.1

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies in serum and multi-organ inflammation. Immune complex deposition in kidney can lead to lupus nephritis, which is a major risk factor for morbidity and mortality in SLE. Using FcγRIIB−/− mice as a lupus animal model, we performed a detailed time course analysis of the extent of the spontaneous leukocyte activation and expansion in spleen and in renal, inguinal, mesenteric lymph nodes. We then correlated the data with the onset of pathology and leukocyte infiltration in the kidney. In the FcγRIIB−/− mouse model, effector-memory CD4 cells and germinal centers appeared first in the spleen and renal lymph nodes, but not in other immune organs such as inguinal or mesenteric lymph nodes. As the disease progresses in these mice, lymphocytes undergo an extensive expansion that involves all immune organs in a systemic manner. At the same moment we can detect the first signs of kidney pathology, measured by histopathology and by the levels of creatinine and albumin in urine. In FcγRIIB−/− mice, the onset of kidney pathology correlates with leukocyte infiltration in kidney, detected both by parenchyma-restricted flow cytometry and histopathology. Macrophages, CD4 and CD8 cells are found both in glomerular and interstitial spaces with the exclusion of B cells, most likely suggesting a role for T cells and/or macrophage specific chemokine signals in lupus nephritic kidney.