Skip to main content
SpringerLink
Log in

Immunobiology of B Cells in Inflammatory Bowel Disease

  • Chapter
  • First Online:
Crohn's Disease and Ulcerative Colitis

Abstract

B cells are an important component of mucosal immune responses in normal and diseased states. Whether B cells play a regulatory or pathogenic role in inflammatory bowel disease (IBD) has not been determined. The pathogenic role of antibodies has been suggested by the frequent presence of circulating antibodies to self- and microbial antigens in IBD. Antibodies could also regulate inflammation through Fc receptors of IgG. Although most studies performed in the experimental models of IBD suggest that B cells suppress mucosal inflammation either by secreting cytokines or by interacting with T cells, a pathogenic role of B cells has been raised in a model of ileitis. An inducible B-cell subset, termed Breg, develops in gut-associated lymphoid tissues under intestinal inflammatory conditions and causes attenuation of colitis through production of a regulatory cytokine IL-10 and by regulating T-cell expansion. An IL-12p70 producing B-cell subset capable of inhibiting colitis has also been identified. Future human studies including functional characterization of mucosal lymphocytes in normal and diseased states are needed to determine whether B cells regulate human intestinal inflammation as shown in the experimental models.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 249.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361:2066–78.

    Article  PubMed  CAS  Google Scholar 

  2. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–34.

    Article  PubMed  CAS  Google Scholar 

  3. Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007;117:514–21.

    Article  PubMed  CAS  Google Scholar 

  4. Bhan AK, Mizoguchi E, Smith RN, Mizoguchi A. Colitis in transgenic and Knockout animals as models of human inflammatory bowel disease. Immunol Rev. 1999;169:195–207.

    Article  PubMed  CAS  Google Scholar 

  5. Mizoguchi A, Mizoguchi E, Bhan AK. Immune networks in animal models of inflammatory bowel disease. Inflamm Bowel Dis. 2003;9:246–59.

    Article  PubMed  Google Scholar 

  6. Mizoguchi A, Mizoguchi E. IBD: past, present and future, lesson from animal models. J Gastroenterol. 2008;43:1–17.

    Article  PubMed  Google Scholar 

  7. Brandtzaeg P, Johansen FE. Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev. 2005;206:32–63.

    Article  PubMed  CAS  Google Scholar 

  8. Noronha AM, Liang YM, Hetzel JT, et al. Hyperactivated B cells in human inflammatory bowel disease. J Leukocyte Biol. 2009;86:1007–16.

    Article  PubMed  CAS  Google Scholar 

  9. Peyrin-Biroulet L, Standaert-Vitse A, Branche J, Chamaillard M. IBD serological panels: facts and perspectives. Inflamm Bowel Dis. 2007;13:1561–6.

    Article  PubMed  Google Scholar 

  10. Ferrante M, Henckaerts L, Joossens M, et al. New serological markers in inflammatory bowel disease are associated with complicated disease behaviour. Gut. 2007;56:1394–403.

    Article  PubMed  Google Scholar 

  11. Brandtzaeg P, Carlsen HS, Halstensen TS. The B-cell system in inflammatory bowel disease. Immune mechanisms in inflammatory bowel disease, Eurekah.com and Springer Science  +  Business Media. 2006:149–167 0-387-30831-8.

    Google Scholar 

  12. Heddle RJ, La Brooy JT, Shearman DJ. Escherichia coli antibody-secreting cells in the human intestine. Clin Exp Immunol. 1982;48:469–76.

    PubMed  CAS  Google Scholar 

  13. Hibi T, Ohara M, Toda K, et al. In vitro anticolon antibody production by mucosal or peripheral blood lymphocytes from patients with ulcerative colitis. Gut. 1990;31:1371–6.

    Article  PubMed  CAS  Google Scholar 

  14. Das KM. Relationship of extraintestinal involvements in inflammatory bowel disease: new insights into autoimmune pathogenesis. Dig Dis Sci. 1999;44:1–13.

    Article  PubMed  CAS  Google Scholar 

  15. Halstensen TS, Das K, Brandtzaeg P. Epithelial deposits of immunoglobulin G1 and activated complement colocalise with the M, 40 kD putative autoantigen in ulcerative colitis. Gut. 1993;34:650–7.

    Article  PubMed  CAS  Google Scholar 

  16. Brandtzaeg P, Korsrud FR. Significance of different J-chain profiles in human tissues; Generation of IgA and IgM with binding site for secretory component is related to the J-chain expressing capacity of the total local immunocyte population, including IgG- and IgD-producing cells, and depends on the clinical state of the tissue. Clin Exp Immunol. 1984;58:709–18.

    PubMed  CAS  Google Scholar 

  17. Kenneth G, Smith C, Clatworthy MR. FcγRIIB in autoimmunity and infection: evolutionary and therapeutic implications. Nat Rev. 2010;10:328–43.

    Article  Google Scholar 

  18. Mizoguchi A, Mizoguchi E, Chiba C, et al. Cytokine imbalance and autoantibody production in T cell receptor-α mutant mice with inflammatory bowel disease. J Exp Med. 1996;183:847–56.

    Article  PubMed  CAS  Google Scholar 

  19. Mizoguchi A, Mizoguchi E, Tonegawa S, Bhan AK. Alteration of a polyclonal to an oligoclonal immune response to cecal aerobic bacterial antigens in TCRα mutant mice with inflammatory bowel disease. Int Immunol. 1996;8:1387–94.

    Article  PubMed  CAS  Google Scholar 

  20. Brandwein SL, McCabe RP, Cong Y, et al. Spontaneously colitic C3H/HeJBir mice demonstrate selective antibody reactivity to antigens of the enteric bacterial flora. J Immunol. 1997;159:44–52.

    PubMed  CAS  Google Scholar 

  21. Mizoguchi A, Mizoguchi E, Smith RN, et al. Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice. J Exp Med. 1997;186:1749–56.

    Article  PubMed  CAS  Google Scholar 

  22. Shimomura Y, Mizoguchi E, Sugimoto K, et al. Regulatory role of B-1 cells in chronic colitis. Int Immunol. 2008;20:729–37.

    Article  PubMed  CAS  Google Scholar 

  23. Elson CO, Cong Y, Qi F, et al. Molecular approaches to the role of the microbiota in inflammatory bowel disease. Ann NY Acad Sci. 2006;1072:39–51.

    Article  PubMed  CAS  Google Scholar 

  24. Targan SR, Landers CJ, Yang H, et al. Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn’s disease. Gastroenterology. 2005;128:2020–8.

    Article  PubMed  CAS  Google Scholar 

  25. Tackenberg B, Jelcic I, Baerenwaldt A, et al. Impaired inhibitory Fcγ receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy. Proc Natl Acad Sci USA. 2009;106:4788–92.

    Article  PubMed  CAS  Google Scholar 

  26. Belostocki K, Pricop L, Redecha PB, et al. Infliximab treatment shifts the balance between stimulatory and inhibitory Fcγ receptor type II isoforms on neutrophils in patients with rheumatoid arthritis. Arthritis Rheum. 2008;58:384–8.

    Article  PubMed  Google Scholar 

  27. Masuda A, Yoshido M, Shiomi H, et al. Fcγ receptor regulation of Citrobacter rodentium infection. Infect Immun. 2008;76:1728–37.

    Article  PubMed  CAS  Google Scholar 

  28. Mizoguchi A, Ogawa A, Takedatsu H, et al. Dependence of intestinal granuloma formation on unique myeloid DC-like cells. J Clin Invest. 2007;117(3):605–15.

    Article  PubMed  CAS  Google Scholar 

  29. McGovern DPB, Gardet A, Torkvist L, et al. Genome-wide association identified multiple ulcerative colitis susceptibility loci. Nat Genet. 2010;42:332–7.

    Article  PubMed  CAS  Google Scholar 

  30. Wolf SD, Dittel BN, Hardardottir F, et al. Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice. J Exp Med. 1996;184:2271–8.

    Article  PubMed  CAS  Google Scholar 

  31. Knoechel B, Lohr J, Kahn E, Abbas AK. The link between lymphocyte deficiency and autoimmunity: roles of endogenous T and B lymphocytes in tolerance. J Immunol. 2005;175:21–6.

    PubMed  CAS  Google Scholar 

  32. Mizoguchi E, Mizoguchi A, Preffer FI, Bhan AK. Regulatory function of mature B cells via costimulatory pathway in a murine colitis model. Int Immunol. 2000;12:597–605.

    Article  PubMed  CAS  Google Scholar 

  33. Blair PA, Noreña LY, Flores-Borja F, et al. CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity. 2010;32:129–40.

    Article  PubMed  CAS  Google Scholar 

  34. Kawamura T, Kanai T, Dohi T, et al. Ectopic CD40 ligand expression on B cells triggers intestinal inflammation. J Immunol. 2004;172:6388–97.

    PubMed  CAS  Google Scholar 

  35. Wei B, Velazquez P, Turovskaya O, et al. Mesenteric B cells centrally inhibit CD4+ T cell colitis through interaction with regulatory T cell subsets. Proc Natl Acad Sci USA. 2005;102:2010–5.

    Article  PubMed  CAS  Google Scholar 

  36. McPherson M, Wei B, Turovskaya O, et al. Colitis immunoregulation by CD8+ T cell requires T cell cytotoxicity and B cell peptide antigen presentation. Am J Physiol Gastrointest Liver Physiol. 2008;295:G485–92.

    Article  PubMed  CAS  Google Scholar 

  37. Munz C. Enhancing immunity through autophagy. Annu Rev Immunol. 2009;27:423–49.

    Article  PubMed  CAS  Google Scholar 

  38. Miller BC, Zhao Z, Stephenson LM, et al. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy. 2008;4:309–14.

    PubMed  CAS  Google Scholar 

  39. Su Y, Carey G, Maric M, Scott DW. B cells induce tolerance by presenting endogenous peptide-IgG on MHC class II molecules via an IFN-gamma-inducible lysosomal thiol reductase-dependent pathway. J Immunol. 2008;181:1153–60.

    PubMed  CAS  Google Scholar 

  40. McCarroll SA, Huett A, Kuballa P, et al. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease. Nat Genet. 2008;40:1107–12.

    Article  PubMed  CAS  Google Scholar 

  41. Izcue A, Coombes JL, Powrie F. Regulatory lymphocytes and intestinal inflammation. Annu Rev Immunol. 2009;27:313–38.

    Article  PubMed  CAS  Google Scholar 

  42. Singh A, Carson 4th WF, Secor Jr ER, et al. Regulatory role of B cells in a murine model of allergic airway disease. J Immunol. 2008;180:7318–26.

    PubMed  CAS  Google Scholar 

  43. Rafei M, Hsieh J, Zehntner S, et al. A granulocyte-macrophage colony-stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties. Nat Med. 2009;15:1038–45.

    Article  PubMed  CAS  Google Scholar 

  44. Moritoki Y, Lian ZX, Lindor K, et al. B-cell depletion with anti-CD20 ameliorates autoimmune cholangitis but exacerbates colitis in transforming growth factor-beta receptor II dominant negative mice. Hepatology. 2009;50:1893–903.

    Article  PubMed  CAS  Google Scholar 

  45. Harris DP, Haynes L, Sayles PC, et al. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol. 2000;1:475–82.

    Article  PubMed  CAS  Google Scholar 

  46. Wojciechowski W, Harris DP, Sprague F, et al. Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus. Immunity. 2009;30:421–33.

    Article  PubMed  CAS  Google Scholar 

  47. Sugimoto K, Ogawa A, Shimomura Y, et al. Inducible IL-12-producing B cells regulate Th2-mediated intestinal inflammation. Gastroenterology. 2007;133:124–36.

    Article  PubMed  CAS  Google Scholar 

  48. Mizoguchi A, Bhan AK. A case for regulatory B cells. J Immunol. 2006;176:705–10.

    PubMed  CAS  Google Scholar 

  49. Mizoguchi A, Mizoguchi E, Takedatsu H, et al. Chronic intestinal inflammatory condition generates IL-10 producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002;16:219–30.

    Article  PubMed  CAS  Google Scholar 

  50. Madan R, Demircik F, Surianarayanan S, Karp CL. Nonredundant roles for B cell-derived IL-10 in immune counter-regulation. J Immunol. 2009;183:2312–20.

    Article  PubMed  CAS  Google Scholar 

  51. Bouaziz JD, Yanaba K, Tedder TF. Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev. 2008;224:201–14.

    Article  PubMed  CAS  Google Scholar 

  52. Jamin C, Morva A, Lemoine S, et al. Regulatory B lymphocytes in humans: a potential role in autoimmunity. Arthritis Rheum. 2008;58:1900–6.

    Article  PubMed  CAS  Google Scholar 

  53. Lund FE, Randall TD. Effector and regulatory B cells: modulators of CD4(+) T cell immunity. Nat Rev Immunol. 2010;10:236–47.

    Article  PubMed  CAS  Google Scholar 

  54. Thaunat O, Morelon E, Defrance T. Am“B”valent: anti-CD20 antibodies unravel the dual role of B cells in immunopathogenesis. Blood. 2010;116:515–21.

    Article  PubMed  CAS  Google Scholar 

  55. Yanaba K, Bouaziz JD, Haas KM, et al. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity. 2008;28:639–50.

    Article  PubMed  CAS  Google Scholar 

  56. Matsushita T, Yanaba K, Bouaziz JD, et al. Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest. 2008;118:3420–30.

    PubMed  CAS  Google Scholar 

  57. Matsushita T, Horikawa M, Iwata Y, Tedder TF. Regulatory B cells (b10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. J Immunol. 2010;185:2240–52.

    Article  PubMed  CAS  Google Scholar 

  58. Shimomura Y, Ogawa A, Kawada M, et al. A unique B-2 B cell subset in the intestine. J Exp Med. 2008;205:1357–68.

    Article  Google Scholar 

  59. Dalwadi H, Wei B, Schrage M, et al. B cell developmental requirement for the G alpha i2 gene. J Immunol. 2003;170:1707–15.

    PubMed  CAS  Google Scholar 

  60. Ostanin DV, Pavlick KP, Bharwani S, et al. T cell-induced inflammation of the small and large intestine in immunodeficient mice. Am J Physiol Gastrointest Liver Physiol. 2006;290:G109–19.

    Article  PubMed  CAS  Google Scholar 

  61. Gerth AJ, Lin L, Neurath MF, et al. An innate cell-mediated, murine ulcerative colitis-like syndrome in the absence of nuclear factor of activated T cells. Gastroenterology. 2004;126:1115–21.

    Article  PubMed  CAS  Google Scholar 

  62. Olson TS, Bamias G, Naganuma M, et al. Expanded B cell population blocks regulatory T cells and exacerbates ileitis in a murine model of Crohn disease. J Clin Invest. 2004;114:389–98.

    PubMed  CAS  Google Scholar 

  63. Dohi T, Fujihashi K, Koga T, et al. T helper type-2 cells induce ileal villus atrophy, goblet cell metaplasia, and wasting disease in T cell-deficient mice. Gastroenterology. 2003;124:672–82.

    Article  PubMed  CAS  Google Scholar 

  64. Mishima Y, Ishihara S, Aziz MM, et al. Decreased production of interleukin-10 and transforming growth factor-beta in Toll-like receptor-activated intestinal B cells in SAMP1/Yit mice. Immunology. 2010;131:473–87.

    Article  PubMed  CAS  Google Scholar 

  65. Fassi DE, Nielsen CH, Kjeldsen J, et al. Ulcerative colitis following B lymphocyte depletion with rituximab in a patient with Graves’ disease. Gut. 2008;57:714–5.

    Article  PubMed  Google Scholar 

  66. Goetz M, Atreya R, Ghalibafian M, et al. Exacerbation of ulcerative colitis after rituximab salvage therapy. Inflamm Bowel Dis. 2007;13:1365–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Harvard University, Massachusetts General Hospital, Immunopathology Unit, Warren 501, 55 Fruit Street, Boston, MA, 02114, USA

    Atsushi Mizoguchi MD, PhD & Atul K. Bhan MBBS, MD

Authors
  1. Atsushi Mizoguchi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atul K. Bhan MBBS, MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Atul K. Bhan MBBS, MD .

Editor information

Editors and Affiliations

  1. Medical School of the Humboldt Universit, Department of Medicine, Charité Medical Center, Virchow Hospita, Berlin, 13344, Germany

    Daniel C. Baumgart

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Mizoguchi, A., Bhan, A.K. (2012). Immunobiology of B Cells in Inflammatory Bowel Disease. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0998-4_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-0998-4_12

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4614-0997-7

  • Online ISBN: 978-1-4614-0998-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation