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

Hidalgo, Yessia; Nunez, Sarah; Jose Fuenzalidal, Maria; Flores-Santibanez, Felipe; Saez, Pablo J.; Dorner, Jessica; Lennon-Dumenil, Ana-Maria; Martinez, Victor; Zorn, Emmanuel; Rosemblatt, Mario; Sauma, Daniela; Rosa Bono, Maria

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 (T-FH). 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-FH 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.

Más información

Título según WOS: ID WOS:000536074900001 Not found in local WOS DB
Título de la Revista: FRONTIERS IN IMMUNOLOGY
Volumen: 11
Editorial: FRONTIERS MEDIA SA
Fecha de publicación: 2020
DOI:

10.3389/fimmu.2020.00696

Notas: ISI