Skip to main content
SpringerLink
Log in

Regulatory B Cells in Mouse Models of Intestinal Inflammation

  • Protocol
  • First Online:
Regulatory B Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1190))

Abstract

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition with increasing incidence and prevalence around the world. Although B cells had generally been believed to play a pathogenic role in IBD due to the production of autoantibodies, a growing body of evidence from mouse models suggests the coexistence of pathogenic B cells and regulatory B cells, termed Breg, in this disorder. Since some unique techniques are required to closely study the Breg in gut-associated lymphoid tissues (GALT), we herein describe how to induce colitis in mice and how to analyze the phenotype and function of GALT-specific Breg.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434

    Article  CAS  PubMed  Google Scholar 

  2. Kaser A, Zeissig S, Blumberg RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28:573–621

    Article  CAS  PubMed  Google Scholar 

  3. Talley NJ, Abreu MT, Achkar JP et al (2011) American College of Gastroenterology IBD Task Force. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol 106:S2–S25

    Article  CAS  PubMed  Google Scholar 

  4. Molodecky NA, Soon IS, Rabi DM et al (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46–54

    Article  PubMed  Google Scholar 

  5. Targan SR, Karp LC (2005) Defects in mucosal immunity leading to ulcerative colitis. Immunol Rev 206:296–305

    Article  CAS  PubMed  Google Scholar 

  6. Mombaerts P, Mizoguchi E, Grusby MJ et al (1993) Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75:274–282

    Article  CAS  PubMed  Google Scholar 

  7. Ma A, Datta M, Margosian E et al (1995) T cells, but not B cells, are required for bowel inflammation in interleukin 2-deficient mice. J Exp Med 182:1567–1572

    Article  CAS  PubMed  Google Scholar 

  8. Mizoguchi A, Mizoguchi E, Smith RN et al (1997) Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice. J Exp Med 186:1749–1756

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Wei B, Velazquez P, Turovskaya O et al (2005) Mesenteric B cells centrally inhibit CD4+ T cell colitis through interaction with regulatory T cell subsets. Proc Natl Acad Sci U S A 102:2010–2015

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Ray A, Basu S, Williams CB et al (2012) A novel IL-10-independent regulatory role for B cells in suppressing autoimmunity by maintenance of regulatory T cells via GITR ligand. J Immunol 188:3188–3198

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Moritoki Y, Lian ZX, Lindor K et al (2009) B-cell depletion with anti-CD20 ameliorates autoimmune cholangitis but exacerbates colitis in transforming growth factor-beta receptor II dominant negative mice. Hepatology 50:1893–1903

    Article  CAS  PubMed  Google Scholar 

  12. Gerth AJ, Lin L, Neurath MF et al (2004) An innate cell-mediated, murine ulcerative colitis-like syndrome in the absence of nuclear factor of activated T cells. Gastroenterology 126:1115–1121

    Article  CAS  PubMed  Google Scholar 

  13. Shinzaki S, Iijima H, Fujii H et al (2012) Altered oligosaccharide structures reduce colitis induction in mice defective in β-1, 4-galactosyltransferase. Gastroenterology 142:1172–1182

    Article  CAS  PubMed  Google Scholar 

  14. Kirkland D, Benson A, Mirpuri J et al (2012) B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage. Immunity 36:228–238

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Mizoguchi A, Mizoguchi E, Takedatsu H et al (2002) Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16:219–230

    Article  CAS  PubMed  Google Scholar 

  16. Sugimoto K, Ogawa A, Shimomura Y et al (2007) Inducible IL-12-producing B cells regulate Th2-mediated intestinal inflammation. Gastroenterology 133:124–136

    Article  CAS  PubMed  Google Scholar 

  17. Mizoguchi E, Mizoguchi A, Preffer FI et al (2000) Regulatory role of mature B cells in a murine model of inflammatory bowel disease. Int Immunol 12:597–605

    Article  CAS  PubMed  Google Scholar 

  18. Mizoguchi A, Bhan AK (2006) A case for regulatory B cells. J Immunol 176:705–710

    Article  CAS  PubMed  Google Scholar 

  19. Schmidt EG, Larsen HL, Kristensen NN et al (2012) B cells exposed to enterobacterial components suppress development of experimental colitis. Inflamm Bowel Dis 18:284–293

    Article  PubMed  Google Scholar 

  20. Yanaba K, Yoshizaki A, Asano Y et al (2011) IL-10-producing regulatory B10 cells inhibit intestinal injury in a mouse model. Am J Pathol 178:735–743

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Dass S, Vital EM, Emery P (2007) Development of psoriasis after B cell depletion with rituximab. Arthritis Rheum 56:2715–2718

    Article  CAS  PubMed  Google Scholar 

  22. Tayal V, Chiu YH, George E et al (2011) Colitis associated with active systemic lupus erythematosus successfully treated with rituximab. J Clin Rheumatol 17:79–82

    Article  PubMed  Google Scholar 

  23. Leiper K, Martin K, Ellis A et al (2011) Randomised placebo-controlled trial of rituximab (anti-CD20) in active ulcerative colitis. Gut 60:1520–1526

    Article  PubMed  Google Scholar 

  24. Goetz M, Atreya R, Ghalibafian M et al (2007) Exacerbation of ulcerative colitis after rituximab salvage therapy. Inflamm Bowel Dis 13:1365–1368

    Article  PubMed  Google Scholar 

  25. El Fassi D, Nielsen CH, Junker P et al (2011) Systemic adverse events following rituximab therapy in patients with Graves’ disease. J Endocrinol Invest 34:e163–e167

    PubMed  Google Scholar 

  26. Ardelean DS, Gonska T, Wires S et al (2010) Severe ulcerative colitis after rituximab therapy. Pediatrics 126:e243–e246

    Article  PubMed  Google Scholar 

  27. Bhalme M, Hayes S, Norton A et al (2013) Rituximab-associated colitis. Inflamm Bowel Dis 19:E41–E43

    Article  PubMed  Google Scholar 

  28. Sekkach Y, Hammi S, Elqatni M et al (2011) Ulcerative colitis: exceptional consequence after rituximab therapy. Ann Pharm Fr 69:265–269

    Article  CAS  PubMed  Google Scholar 

  29. Nishida A, Nagahama K, Imaeda H et al (2012) Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells. J Exp Med 209:2383–2394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Bouabe H (2012) Cytokine reporter mice: the special case of IL-10. Scand J Immunol 75:553–567

    Article  CAS  PubMed  Google Scholar 

  31. Madan R, Demircik F, Surianarayanan S et al (2009) Nonredundant roles for B cell-derived IL-10 in immune counter-regulation. J Immunol 183:2312–2320

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Mizoguchi A (2012) Animal models of inflammatory bowel disease. Prog Mol Biol Transl Sci 105:263–320

    Article  CAS  PubMed  Google Scholar 

  33. Mishima Y, Ishihara S, Aziz MM et al (2010) Decreased production of interleukin-10 and transforming growth factor-beta in Toll-like receptor-activated intestinal B cells in SAMP1/Yit mice. Immunology 131:473–487

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Shimomura Y, Mizoguchi E, Sugimoto K et al (2008) Regulatory role of B-1 B cells in chronic colitis. Int Immunol 20:729–737

    Article  CAS  PubMed  Google Scholar 

  35. Shimomura Y, Ogawa A, Kawada M et al (2008) A unique B2 B cell subset in the intestine. J Exp Med 205:1343–1355

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Mauri C, Bosma A (2012) Immune regulatory function of B cells. Annu Rev Immunol 30:221–241

    Article  CAS  PubMed  Google Scholar 

  37. Mackay F, Figgett WA, Saulep D et al (2010) B-cell stage and context-dependent requirements for survival signals from BAFF and the B-cell receptor. Immunol Rev 237:205–225

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study has been supported primarily by NIH RO1AI081807 and partially by RO1DK091247.

Author information

Authors and Affiliations

  1. Molecular Pathology Unit, Massachusetts General Hospital, 149 CNY-6024, 13th Street, Charlestown, MA, 02114, USA

    Atsushi Nishida

  2. Gastroenterology Division, Massachusetts General Hospital, 149 CNY-6024, 13th Street, Charlestown, MA, 02114, USA

    Atsushi Nishida

  3. Department of Pathology, Harvard Medical School, Boston, MA, USA

    Atsushi Nishida

  4. Gastrointestinal Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA

    Emiko Mizoguchi

  5. Molecular Pathology Unit, Massachusetts General Hospital, 149 CNY-6024, 13th Street, Charlestown, MA, 02129, USA

    Cindy W. Lau & Atsushi Mizoguchi

  6. Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA

    Emiko Mizoguchi

  7. Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA

    Cindy W. Lau & Atsushi Mizoguchi

Authors
  1. Atsushi Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cindy W. Lau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emiko Mizoguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Atsushi Mizoguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Atsushi Mizoguchi .

Editor information

Editors and Affiliations

  1. Department of Medical and Biological Sciences, University of Udine, Udine, Italy

    Gaetano Vitale

  2. Department of Medical and Biological Sciences, University of Udine, Udine, Italy

    Francesca Mion

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Nishida, A., Lau, C.W., Mizoguchi, E., Mizoguchi, A. (2014). Regulatory B Cells in Mouse Models of Intestinal Inflammation. In: Vitale, G., Mion, F. (eds) Regulatory B Cells. Methods in Molecular Biology, vol 1190. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1161-5_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1161-5_16

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1160-8

  • Online ISBN: 978-1-4939-1161-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation