TY - JOUR
T1 - Thymic B Cells Promote Germinal Center-Like Structures and the Expansion of Follicular Helper T Cells in Lupus-Prone Mice
AU - Hidalgo, Yessia
AU - Núñez, Sarah
AU - Fuenzalida, Maria Jose
AU - Flores-Santibáñez, Felipe
AU - Sáez, Pablo J.
AU - Dorner, Jessica
AU - Lennon-Dumenil, Ana Maria
AU - Martínez, Victor
AU - Zorn, Emmanuel
AU - Rosemblatt, Mario
AU - Sauma, Daniela
AU - Bono, Maria Rosa
N1 - Publisher Copyright:
© Copyright © 2020 Hidalgo, Núñez, Fuenzalida, Flores-Santibáñez, Sáez, Dorner, Lennon-Dumenil, Martínez, Zorn, Rosemblatt, Sauma and Bono.
PY - 2020/4/28
Y1 - 2020/4/28
N2 - 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.
AB - 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.
KW - follicular helper T cells
KW - germinal center
KW - plasma cells
KW - systemic lupus erythematosus
KW - thymic B cells
UR - http://www.scopus.com/inward/record.url?scp=85084551695&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.00696
DO - 10.3389/fimmu.2020.00696
M3 - Article
C2 - 32411134
AN - SCOPUS:85084551695
SN - 1664-3224
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 696
ER -