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Recent advances in regulatory T cells induced by B cells

Cellular & Molecular Immunology volume 15, pages 539–541 (2018)Cite this article

Naïve CD4+CD25− T cells activated in the presence of naïve splenic B cells may differentiate into CD4+CD25+Foxp3− regulatory T cells, which were named Treg-of-B cells by our group (Table 1). In addition, the oral delivery of antigen-activated naive Peyer’s patch B cells induced Treg-of-B(P) cells with an increased suppressive function.3 Our recent article reported that peritoneal B-1a cells produced more IL-10; moreover, B-1a cells promoted the induction of Treg-of-B1a cells in an IL-10-independent manner.1 In our studies, splenic B2-cell-induced Treg-of-B cells, Peyer’s patch B-cell-induced Treg-of-B (P) and peritoneal B-1a-cell-induced Treg-of-B1a cells shared similar phenotypes and functions. Our group subsequently reported that adoptive transfer these Treg-of-B cells protected mice from several disease models, including allergic asthma, rheumatoid arthritis and inflammatory bowel disease. Here, we summarize the suppression and induction mechanism of Treg-of-B cells (Figure 1).

We and other groups have demonstrated that antigen-presenting B cells may play a critical role in tolerance. Oral delivery of antigen-activated Peyer’s patch B cells induced Treg-of-B(P) cells with enhanced suppressive ability.3 Furthermore, oral delivery antigen-activated CD4+CD25+ T cells, similar to B-cell-induced Treg-of-B cells, increased the levels of CTLA4, ICOS and PD1 and improved their suppressive functions. Both the oral delivery of antigen and adoptive transfer of single antigen-specific Treg-of-B cells protected mice from allergic asthma in antigen-specific and non-antigen-specific fashions.2 Consistent with these findings, lentiviral-enforced collagen peptide-presenting B cells protected mice from collagen-induced arthritis, which may, in part, involve the induction of CD4+ regulatory T cells.10 These studies indicated that B cells possess an ability to promote the generation of CD4+ regulatory T cells as part of the sophisticated tolerance mechanism.

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References

  1. Hsu LH, Li KP, Chu KH, Chiang BL. A B-1a cell subset induces Foxp3(−) T cells with regulatory activity through an IL-10-independent pathway. Cell Mol Immunol 2015; 12: 354–365.

    Article  CAS  Google Scholar 

  2. Chien CH, Yu HH, Chiang BL. Single allergen-induced oral tolerance inhibits airway inflammation in conjugated allergen immunized mice. J Allergy Clin Immunol 2015; 136: 1110–1113.e1114.

    Article  CAS  Google Scholar 

  3. Chu KH, Chiang BL. Regulatory T cells induced by mucosal B cells alleviate allergic airway hypersensitivity. Am J Respir Cell Mol Biol 2012; 46: 651–659.

    Article  CAS  Google Scholar 

  4. Chu KH, Chiang BL. Characterization and functional studies of forkhead box protein 3(-) lymphocyte activation gene 3(+) CD4(+) regulatory T cells induced by mucosal B cells. Clin Exp Immunol 2015; 180: 316–328.

    Article  CAS  Google Scholar 

  5. Chen SY, Hsu WT, Chen YL, Chien CH, Chiang BL. Lymphocyte-activation gene 3(+) (LAG3(+)) forkhead box protein 3(−) (FOXP3(−)) regulatory T cells induced by B cells alleviates joint inflammation in collagen-induced arthritis. J Autoimmun 2016; 68: 75–85.

    Article  CAS  Google Scholar 

  6. Chien CH, Yu HC, Chen SY, Chiang BL. Characterization of c-Maf+Foxp3- regulatory T cells induced by repeated stimulation of antigen-presenting B cells. Sci Rep 2017; 7: 46348.

    Article  CAS  Google Scholar 

  7. Shao TY, Hsu LH, Chien CH, Chiang BL. Novel Foxp3(−) IL-10(−) regulatory T-cells induced by B-cells alleviate intestinal inflammation in vivo. Sci Rep 2016; 6: 32415.

    Article  CAS  Google Scholar 

  8. Reichardt P, Dornbach B, Rong S, Beissert S, Gueler F, Loser K et al. Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse. Blood 2007; 110: 1519–1529.

    Article  CAS  Google Scholar 

  9. Etemire E, Krull M, Hasenberg M, Reichardt P, Gunzer M. Transiently reduced PI3K/Akt activity drives the development of regulatory function in antigen-stimulated naive T-cells. PLoS One 2013; 8: e68378.

    Article  CAS  Google Scholar 

  10. Andersson SE, Eneljung T, Tengvall S, Jirholt P, Stern A, Henningsson L et al. Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis. Arthritis Res Ther 2016; 18: 140.

    Article  Google Scholar 

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Authors and Affiliations

  1. Graduate Institute of Clinical Medicine, National Taiwan University, 10048, Taipei, Taiwan, China

    Chien-Hui Chien & Bor-Luen Chiang

  2. Department of Medicinal Research, National Taiwan University Hospital, 10002, Taipei, Taiwan, China

    Bor-Luen Chiang

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Correspondence to Bor-Luen Chiang.

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Chien, CH., Chiang, BL. Recent advances in regulatory T cells induced by B cells. Cell Mol Immunol 15, 539–541 (2018). https://doi.org/10.1038/cmi.2017.130

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