Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of autoreactive T and B cells, autoantibody production, and immune complex deposition in various organs. Previous evidence showed abnormal accumulation of B cells in the thymus of lupus-prone mice, but the role of this population in the progression of the disease remains mostly undefined. Here we analyzed the spatial distribution, function, and properties of this thymic B cell population in the BWF1 murine model of SLE. We found that in diseased animals, thymic B cells proliferate, and cluster in structures that resemble ectopic germinal centers. Moreover, we detected antibody-secreting cells in the thymus of diseased-BWF1 mice that produce anti-dsDNA IgG autoantibodies. We also found that thymic B cells from diseased-BWF1 mice induced the differentiation of thymocytes to follicular helper T cells (TFH). These data suggest that the accumulation of B cells in the thymus of BWF1 mice results in the formation of germinal center-like structures and the expansion of a TFH population, which may, in turn, activate and differentiate B cells into autoreactive plasma cells. Therefore, the thymus emerges as an important niche that supports the maintenance of the pathogenic humoral response in the development of murine SLE.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a set of clinical abnormalities ranging from mild symptoms such as malaise, arthritis, or dermatitis to more severe manifestations such as renal disease or compromise of the central nervous system
Fluorescent co-staining of CD4, CD8, and CD19 confirmed that the thymus of diseased mice is characterized by the presence of large B cell clusters and the absence of CD4+CD8+ double- positive (DP) thymocytes (Figure 1C) which are normally found in the cortex [27]
SLE is a chronic autoimmune disease of unknown etiology characterized by the formation of immune complexes, which are deposited in tissues causing inflammation
Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a set of clinical abnormalities ranging from mild symptoms such as malaise, arthritis, or dermatitis to more severe manifestations such as renal disease or compromise of the central nervous system. The thymus is a primary lymphoid organ whose main function is the induction of immune self-tolerance to prevent autoimmunity This organ is dedicated to T cell generation and maturation, a function that usually declines with age and can be severely compromised in autoimmune diseases [3]. There have been reports of patients with other autoimmune diseases, such as ulcerative colitis and systemic lupus erythematosus that present abnormalities in the structure of the thymus [7,8,9]. It is unknown if these changes contribute to the disease
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