调节性B细胞课件

1、Bregs-Regulatory B cells,1,学习交流PPT,Introduction,1,Clues to Bregs existence,2,Development and differentiation,3,4,Contents,Phenotypical Identification,6,Bregs in diseases,Function of Bregs,5,2,学习交流PPT,Introduction,Traditionally, Bcells have been thought to contribute to disease through production of

2、antibodies In the past two decades, investigators have attributed additional functions to B cells, including antigen presentation, the production of multiple cytokines Recently, the ability of Bcells to negatively regulate cellular immune responses and inflammation has been described and the concept

3、 of regulatory Bcells has emerged.,3,学习交流PPT,Clues to Bregs existence,2002,B cells suppress DTH,IL-10-producing B cells regulate autoimmunity CD19+CD1dhi B cells producing IL-10 control Th2-driven colitis,the term “regulatory B cells”, which defines B-cell subsets with regulatory properties, was fir

4、st introduced,B celldecient mice develop chronic EAE,B cells could restrain the severity of autoimmune disease,1980,antigen-activated B cells could induce tolerance in recipient naive mice,Support a suppressive framework for B cells and introduce a link with T-cell tolerance,4,学习交流PPT,Development an

5、d Differentiation,在骨髓发育，分布外周淋巴器官， 参与特异性免疫,定位于大网膜、胸腔及肠黏膜固有层， 参与非特异性免疫,5,学习交流PPT,Development and Differentiation,FO B cell,T2 MZP B cell,MZ B cell,LeBien TW, Tedder TF. B lymphocytes: how they develop and function. Blood. 2008,6,学习交流PPT,Development and Differentiation,7,学习交流PPT,Development and Differe

6、ntiation,Mauri C, Ehrenstein MR. The short history of regulatory B cells. Trends Immunol. 2008,8,学习交流PPT,Development and Differentiation,Mauri C, Ehrenstein MR. The short history of regulatory B cells. Trends Immunol. 2008,9,学习交流PPT,Development and Differentiation,Mizoguchi A, Bhan AK. A case for re

7、gulatory B cells. J Immunol. 2006,10,学习交流PPT,Phenotypical Identification,He Y. The roles of regulatory B cells in cancer. J Immunol Res. 2014.,11,学习交流PPT,Phenotypical Identification,Mauri C. Immune regulatory function of B cells. Annu Rev Immunol. 2012,12,学习交流PPT,Phenotypical Identification,Mauri C.

8、 Immune regulatory function of B cells. Annu Rev Immunol. 2012,13,学习交流PPT,Phenotypical Identification,Bodhankar S. IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke. Metab Brain Dis. 2013,14,学习交流PPT,Phenotypical Identification,There is no unique marker, or set

9、of markers, that exclusively identifies the Bregs There is no master regulator transcription factor identified in Breg development IL-10 secretion is still a vital standard in the identification of Bregs,15,学习交流PPT,Function of Bregs,Mizoguchi A, Bhan AK. A case for regulatory B cells. J Immunol. 200

10、6,16,学习交流PPT,Function of Bregs,Mauri C. Immune regulatory function of B cells. Annu Rev Immunol. 2012,17,学习交流PPT,Function of Bregs,Mauri C. Immune regulatory function of B cells. Annu Rev Immunol. 2012,18,学习交流PPT,Mauri C. Immune regulatory function of B cells. Annu Rev Immunol. 2012,Function of Breg

11、s,19,学习交流PPT,Bregs in autoimmunity,Experimental autoimmune encephalomyelitis (EAE) Inflammatory Bowel Disease (IBD) Rheumatoid Arthritis (RA),20,学习交流PPT,Bregs in autoimmunityEAE,B-cell-deficient mice (mMT) failed to control EAE, and unlike the wild-type mice, did not undergo spontaneous remission,In

12、 the absence of IL-10 production by B cells, the pro- inflammatory type 1 immune response persisted and mice did not recover,Lack of disease resolution was attributed to the inability of T cells to switch to a protective Th2 response,21,学习交流PPT,Bregs in autoimmunityIBD,mMT TCRa-/- mice manifest an e

13、arlier onset of disease and an exacerbated intestinal inammation compared with the TCRa-/-mice,The amelioration of disease was paralleled by an increase in the clearance of apoptotic cells, suggesting an autoantibody-mediated protective mechanism,Administration of purified immunoglobulin from TCRa-/

14、- mice with a mixture of monoclonal autoantibodies attenuate colitis,22,学习交流PPT,Bregs in autoimmunityRA,Stimulation of arthritogenic B cells with an agonistic anti-CD40 and collagen generated a subset of B cells producing IL-10,This suppressive effect was associated with a downregulation of Th1 cyto

15、kines and was dependent upon the release of IL-10,Transfer of collagen and anti-CD40-stimulated B cells to syngeneic immunized mice prevented the induction of arthritis and ameliorated established disease,23,学习交流PPT,Bregs in cancer,Bregs support lung metastases via Treg generation,Olkhanud PB. Tumor

16、-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4+ T cells to T-regulatory cells. Cancer Res. 2011,24,学习交流PPT,Bregs in cancer,Bregs support lung metastases via Treg generation,Olkhanud PB. Tumor-evoked regulatory B cells promote breast cancer metastasis by convert

17、ing resting CD4 T cells to T-regulatory cells. Cancer Res. 2011,25,学习交流PPT,Bregs in cancer,Regulatory B cell production of IL-10 inhibits lymphoma depletion during CD20 immunotherapy,Horikawa M. Regulatory B cell production of IL-10 inhibits lymphoma depletion during CD20 immunotherapy in mice. J Cl

18、in Invest. 2011,26,学习交流PPT,Bregs in transplantationGVHD,Rowe V.Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation. Blood. 2006,Acute GVHD is initially augmented in mMT recipients relative to wild-type recipients as a result of an increase i

19、n donor T-cell proliferation, expansion, and inflammatory cytokine production,Recipient mice in which B cells are unable to produce IL-10 develop more severe acute GVHD than recipient mice in which B cells are wild type,TBI deplete most B cell but rapidly induces sustained interleukin-10 generation

20、from B cells,27,学习交流PPT,Outstanding questions and Futurue directions,we need to better identify surface markers that, coupled with transcriptional factors, would provide a unique signature The question of whether all B cells producing IL-10, irrespective of their phenotype, are capable of suppressio

21、n or whether multiple Breg subsets exist and if they are all equipollent is yet to be determined,28,学习交流PPT,Outstanding questions and Futurue directions,We need to better identify surface markers that, coupled with transcriptional factors, would provide a unique signature The question of whether all B cells producing IL