The B-Cell System in Inflammatory Bowel Disease
Per Brandtzaeg, Hege S. Carlsen and Trond S. Halstensen
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.