Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice

• Published in: Frontiers in immunology Vol. 11; p. 696
• Main Authors: Hidalgo, Yessia, Núñez, Sarah, Fuenzalida, Maria Jose, Flores-Santibáñez, Felipe, Sáez, Pablo J, Dorner, Jessica, Lennon-Dumenil, Ana-Maria, Martínez, Victor, Zorn, Emmanuel, Rosemblatt, Mario, Sauma, Daniela, Bono, Maria Rosa
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 28.04.2020
• Subjects: Animals; Autoantibodies - immunology; B-Lymphocytes - immunology; Cell Differentiation; Cells, Cultured; Coculture Techniques; Disease Models, Animal; DNA - immunology; Female; follicular helper T cells; germinal center; Germinal Center - immunology; Immunity, Humoral; Immunology; Lupus Erythematosus, Systemic - immunology; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred NZB; plasma cells; Plasma Cells - immunology; systemic lupus erythematosus; T Follicular Helper Cells - immunology; thymic B cells; Thymus Gland - immunology; systemic lupus erythematosus; thymic B cells; germinal center; follicular helper T cells; plasma cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.00696

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 (T ). 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 T 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.