title: Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis.
abstract: This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19(+)CD5(+)CD1d(high) B cell subset that may play a critical role in the maintenance of immune homeostasis. Indeed, this population was identified in the murine thymus, and furthermore, when cocultured with CD4(+) T cells, this population of B cells supported the maintenance of CD4(+)Foxp3(+) Tregs in vitro, in part, via the CD5-CD72 interaction. Mice homozygous for Cd19(Cre) (CD19(-/-)) express B cells with impaired signaling and humoral responses. Strikingly, CD19(-/-) mice produce fewer CD4(+)Foxp3(+) Tregs and a greater percentage of CD4(+)CD8(-) and CD4(-)CD8(+) T cells. Consistent with these results, transfer of thymic CD19(+)CD5(+)CD1d(hi) B cells into CD19(-/-) mice resulted in significantly up-regulated numbers of CD4(+)Foxp3(+) Tregs with a concomitant reduction in CD4(+)CD8(-) and CD4(-)CD8(+) T cell populations in the thymus, spleen, and LNs but not in the BM of recipient mice. In addition, thymic CD19(+)CD5(+)CD1d(hi) B cells significantly suppressed autoimmune responses in lupus-like mice via up-regulation of CD4(+)Foxp3(+) Tregs and IL-10-producing Bregs. This study suggests that thymic CD19(+)CD5(+)CD1d(hi)IL-10(+) Bregs play a critical role in the maintenance of immune homeostasis.
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xing
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Mingke
authors.initials: M
authors.lastname: Zheng
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China wang_renxi@yahoo.com liyan62033@gmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: *Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China wang_renxi@yahoo.com liyan62033@gmail.com.
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D007109:Immunity; D019426:Integrases / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D013950:Thymus Gland / Q000166:cytology*; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10; C045073:Cre recombinase; D019426:Integrases
keywords: CD72; Foxp3; regulatory T cells