Therapeutic B cell depletion impairs adaptive and autoreactive CD4+ T cell activation in mice.
CD20 antibody depletion of B lymphocytes effectively ameliorates multiple T cell-mediated autoimmune diseases through mechanisms that remain unclear. To address this, a mouse CD20 antibody that depletes >95% of mature B cells in mice with otherwise intact immune systems was used to assess the role of B cells in CD4(+) and CD8(+) T cell activation and expansion in vivo. B cell depletion had no direct effect on T cell subsets or the activation status of CD4(+) and CD8(+) T cells in naive mice. However, B cell depletion impaired CD4(+) T cell activation and clonal expansion in response to protein antigens and pathogen challenge, whereas CD8(+) T cell activation was not affected. In vivo dendritic cell ablation, along with CD20 immunotherapy, revealed that optimal antigen-specific CD4(+) T cell priming required both B cells and dendritic cells. Most importantly, B cell depletion inhibited antigen-specific CD4(+) T cell expansion in both collagen-induced arthritis and autoimmune diabetes mouse models. These results provide direct evidence that B cells contribute to T cell activation and expansion in vivo and offer insights into the mechanism of action for B cell depletion therapy in the treatment of autoimmunity.
Bouaziz
Jean-David
JD
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Yanaba
Koichi
K
Venturi
Guglielmo M
GM
Wang
Yaming
Y
Tisch
Roland M
RM
Poe
Jonathan C
JC
Tedder
Thomas F
TF
D000818:Animals; D017951:Antigen Presentation; D018951:Antigens, CD20 / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic
D018951:Antigens, CD20; D007376:Interleukin-2; D019041:L-Selectin; D007371:Interferon-gamma