Regulatory B Cells Induce Formation of IL-10-Expressing T Cells in Mice with Autoimmune Neuroinflammation.
Although B cells are traditionally known for their role in propagating proinflammatory immune responses, their immunosuppressive effects have only recently begun to be appreciated. How these regulatory B cells (Bregs) suppress the immune response remains to be worked out in detail. In this article, we show that Bregscan induce the formation of conventional FoxP3+regulatory T cells (Tregs), as well as a more recently described CD49b+CD223+regulatory T-cell subset, known as type 1 regulatory T cells (Tr1s). When Bregsare transferred into mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, they home to the spleen and mesenteric lymph nodes, leading to an expansion of Tregsand Tr1 in vivo Tregsand Tr1s are also found in greater proportions in the CNS of mice with EAE treated with Bregsand are correlated with the remission of symptoms. The discovery that Bregsinduce the formation of regulatory T-cell subsets in vivo may herald their use as immunosuppressive agents in adoptive cellular therapies for autoimmune pathologies.



Although B cells are traditionally known for their role in propagating proinflammatory immune responses, their immunosuppressive effects have only recently begun to be appreciated. How regulatory B cells (Bregs) suppress the immune response remains to be fully understood. In this article, we show that Bregscan induce the formation of conventional regulatory T cells (Tregs) as well as type 1 regulatory T cells (Tr1s). When Bregsare transferred into mice with experimental autoimmune encephalomyelitis (EAE), they home to secondary lymphoid organs, leading to an expansion of Tregsand Tr1s in vivo Tregsand Tr1s are also found in greater proportions in the CNS of mice with EAE treated with Bregsand are correlated with the remission of symptoms.
Department of Medicine, University of Wisconsin School of Medicine and Public Health and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin 53706.
Andrea
0000-0001-6211-7480
A
Pennati
Departments of Hematology and Medical Oncology.
Spencer
S
Ng
Neurology, and.
Yuanqiang
Y
Wu
Departments of Hematology and Medical Oncology.
Jordan R
JR
Murphy
Departments of Hematology and Medical Oncology.
Jiusheng
0000-0003-1758-3778
J
Deng
Microbiology and Immunology, Emory University, Atlanta, Georgia 30322, and.
Srikant
0000-0003-2765-1500
S
Rangaraju
Microbiology and Immunology, Emory University, Atlanta, Georgia 30322, and.
Seneshaw
S
Asress
Department of Oncology, Second Xiangya Hospital, Changsha 410011, Hunan, People's Republic of China.
Jennifer L
0000-0002-9461-9431
JL
Blanchfield
Department of Oncology, Second Xiangya Hospital, Changsha 410011, Hunan, People's Republic of China.
Brian
B
Evavold
Department of Medicine, University of Wisconsin School of Medicine and Public Health and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin 53706, jgalipeau@wisc.edu.
Jacques
0000-0002-9374-1996
J
Galipeau
D019264:Adoptive Transfer; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002675:Child, Preschool; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D007962:Leukocytes / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D016753:Interleukin-10