B Lymphocyte intestinal homing in inflammatory bowel disease

Abstract

BackgroundInflammatory bowel disease (IBD) is thought to be due to an abnormal interaction between the host immune system and commensal microflora. Within the intestinal immune system, B cells produce physiologically natural antibodies but pathologically atypical anti-neutrophil antibodies (xANCAs) are frequently observed in patients with IBD. The objective is to investigate the localisation of immunoglobulin-producing cells (IPCs) in samples of inflamed intestinal tissue taken from patients with IBD, and their possible relationship with clinical features.MethodsThe IPCs in small intestinal, colonic and rectal biopsy specimens of patients with IBD were analysed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The B cell phenotype of the IPC-positive samples was assessed using monoclonal antibodies specific for CD79, CD20, CD23, CD21, CD5, λ and κ chains. Statistical correlations were sought between the histological findings and clinical expression.ResultsThe study involved 96 patients (64 with ulcerative colitis and 32 with Crohn's disease). Two different patterns of B lymphocyte infiltrates were found in the intestinal tissue: one was characterised by a strong to moderate stromal localisation of small IgM+/CD79+/CD20-/CD21-/CD23-/CD5± IPCs (42.7% of cases); in the other (57.3%) no such small IPCs were detected in stromal or epithelial tissues. IPCs were significantly less frequent in the patients with Crohn's disease than in those with ulcerative colitis (p = 0.004).ConclusionOur findings suggest that different immunopathogenetic pathways underlie chronic intestinal inflammation with different clinical expressions. The presence of small B lymphocytes resembling B-1 cells also seemed to be negatively associated with Crohn's disease. It can therefore be inferred that the gut contains an alternative population of B cells that have a regulatory function.

Morphological distribution of μ chains and cd15 receptors in colorectal polyp and adenocarcinoma specimens

“…We have recently investigated the localisation of immunoglobulin-producing cells (IPCs) in inflamed intestinal tissue samples from 96 patients with inflammatory bowel disease (IBD: 64 with ulcerative colitis [UC] and 32 with Crohn’s disease [CD]), and identified two main patterns of B lymphocyte infiltration. One (42.7% of the cases) was characterised by the moderate-strong stromal localisation of small B1 cell-like IgM+/CD79+/CD20-/CD21-/CD23-/CD5 ± IPCs [8], and the other (35.4% of the cases) by the peri-glandular localisation of IPCs with irregular nuclei that had surface markers specific for a B cell subset (IgM and CD79), but quantitative differences in their λ and κ chains. The same 96 patients were also tested for CD15+ receptors, which were localised on inflammatory cell surfaces or in the crypts of the intestinal epithelium [9].…”

Enteroantigen (eAg)-binding B lymphocytes in the mouse - phenotype, distribution, function and eAg-specific antibody secretion

“…In general, B cells are regarded as being protective in IBD, as B cell depletion therapies to treat conditions such as Graves disease have lead to the development (1) or exacerbation of IBD (2). Moreover, absence of immunoglobulin-producing B cells in the intestinal epithelium was found to correlate with a disease aggravation in IBD patients (49) and a B cell-deficient mouse model of primary biliary cirrhosis develops severe colitis, which can be diminished by transplantation of peritoneal B cells from healthy mice (8).…”

“…(B) Splenic B cells from either B6 or MD4 mice were exposed to eAg, and then their capacity to stimulate T cell proliferation according to APC: T cell ratio was determined at the 5th day of co-culture through scintillation counting (cpm (22). Clinically, the absence of B1-like B cells in intestinal biopsies from IBD patients correlated with a more severe disease history (49). Recently, the chemokine scavenger receptor D6 has been proposed as a pan innate-like B cell marker, but as no reliable commercial antibody exists against mouse D6 (50), a FCM analysis of D6 expression was out of our reach.…”

B1a Lymphocytes (CD19+CD5+) Deficiency in Patients with Crohn’s Disease and Its Relation with Disease Severity

“…Only a single article reported that granulomas in the mesenteric lymph nodes of patients with CD are composed of centrally located T-lymphocytes and of epithelioid cells, which are of a monocyte/macrophage origin and have the characteristics of antigen-presenting cells, while at the periphery of the granulomas a lymphocytic corona composed of Ba1+, B1+ B lymphocytes may be present [22]. Defendenti et al [23] showed that only 20% of CD patients displayed infiltration of B1 cells in their tissues, while this percentage reached 70% in ulcerative colitis. Subsequently, the presence of small B-lymphocytes resembling B-1 cells could also be negatively associated with CD.…”