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Immune Mechanisms in Inflammatory Bowel Disease pp 149–167Cite as

The B-Cell System in Inflammatory Bowel Disease

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 579))

Abstract

Secretory immunity is the best-defined part of the mucosal immune system. This adaptive humoral defense mechanism depends on a fine-tuned cooperation between secretory epithelia and local plasma cells. Such mucosal immunocytes produce preferentially dimers and larger polymers of immunoglobulin A (collectively called pIgA), which contain J chain and therefore can bind to the epithelial secretory component (SC). This transmembrane glycoprotein functions as pIg receptor (pIgR) that also translocates pentameric IgM to the epithelial surface. B cells with a high level of J-chain expression and pIg-pIgR interactions at mucosal effector sites are thus necessary for the generation of secretory antibodies (SIgA and SIgM).

Secretory antibodies perform immune exclusion in a first-line defense, thereby counteracting microbial colonization and mucosal penetration of soluble antigens. However, local production of pIgA is significantly down-regulated in inflammatory bowel disease (IBD), as revealed by strikingly decreased J-chain expression. Although the total increase of the immunocyte population in IBD lesions probably compensates for the relatively reduced pIgA production, decreased pIgR/SC expression in regenerating and dysplastic epithelium signifies that the SIgA system is topically deficient. There is, moreover, a significant shift from IgA2 to IgA1 production, the latter subclass being less resistant to proteolytic degradation. These changes—together with activation of mucosal macrophages and a dramatic increase of IgG-producing cells—may reflect local establishment of a second defense line which, however, is unsuccessful in its attempt to eliminate antigens derived from the indigenous microbial flora. Such a ‘frustrated’ local humoral immune system results in altered immunological homeostasis and jeopardized mucosal integrity.

Complement activation observed in relation to epithelium-bound IgG1 in ulcerative colitis indicates, moreover, that the surface epithelium is subjected to immunological attack by an autoimmune reaction. These luminal deposits regularly contain terminal cytotoxic complement, and often also C3b as a sign of persistent activation. Comparison of identical twins, discordant with regard to ulcerative colitis, suggests that the markedly skewed local IgG1 response seen in this IBD entity may be genetically determined.

The initial event(s) eliciting B-cell driven immunopathology in IBD remains unknown. Abrogation of oral tolerance to certain antigens from commensal bacteria has been suggested as a putative early mechanism, and lymphoid neogenesis and hyperplasia in the lesions most likely signify massive microbial overstimulation of the local B-cell system. Such ectopic lymphoid microcompartments may contribute substantially to the proinflammatory systemic-type of B-cell responses occurring in established IBD lesions.

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Authors and Affiliations

  1. Laboratory for Immunohistochemistry and Immunopathology (LIIPAT) Institute of Pathology, University of Oslo, Oslo, Norway

    Per Brandtzaeg & Hege S. Carlsen

  2. Institute of Oral Biology, University of Oslo, Rikshospitalet, Oslo, Norway

    Trond S. Halstensen

Authors
  1. Per Brandtzaeg
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  2. Hege S. Carlsen
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  3. Trond S. Halstensen
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Editors and Affiliations

  1. Gastroenterology Division and Laboratory of Mucosal Immunology, Brigham and Women’s Hospital, Harvard, Massachusetts, USA

    Richard S. Blumberg

  2. 1st Department of Medicine, Johannes-Gutenberg-University, Mainz, Germany

    Markus F. Neurath

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Brandtzaeg, P., Carlsen, H.S., Halstensen, T.S. (2006). The B-Cell System in Inflammatory Bowel Disease. In: Blumberg, R.S., Neurath, M.F. (eds) Immune Mechanisms in Inflammatory Bowel Disease. Advances in Experimental Medicine and Biology, vol 579. Springer, New York, NY. https://doi.org/10.1007/0-387-33778-4_10

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