Unusual B cell morphology in inflammatory bowel disease

Abstract

B lymphocytes express various different types of surface immunoglobulins that are largely unrelated to other hematological lines, although some reports have described a relationship between malignant B cells and other cells such as macrophages. Multiple genes of hematopoietic lineage, including transcription factors, are co-expressed in hematopoietic stem cells and progenitors, a phenomenon referred to as "lineage priming". Changes in the expression levels and timing of transcription factors can induce the lineage conversion of committed cells, which indicates that the regulation of transcription factors might be particularly critical for maintaining hierarchical hematopoietic development. The aim of this study was to evaluate the surface markers of particular IgM-positive and irregularly nucleated cells detected in patients with inflammatory bowel disease (IBD), and to assess their association with diagnosis and inflammatory cell recruitment. Small intestine, colon and rectal biopsy specimens of 96 IBD patients were studied. Immunoglobulin-producing cells (IPCs) were analyzed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The specimens positive for B cells with irregular nuclei were assessed using monoclonal antibodies specific for CD79, and λ and κ chains in order to confirm their B cell nature. CD15+ cells, an important marker of inflammatory cell recruitment, were also evaluated. Statistical correlations were sought between the histological findings and clinical expression. 34 (35.4%) of the 96 patients (64 with ulcerative colitis and 32 with Crohn's disease) presented a periglandial localization of IPCs with irregular nuclei, which showed surface markers specific for the B cell subset, such as IgM and CD79, but quantitative differences in λ and κ chains. These specimens also contained CD15-positive cells, which are usually absent in healthy controls. The quantitative aspects and localization of the CD15-positive cells correlated with the distribution of the IPCs with irregular nuclei. IPCs with irregular nuclei were significantly more frequent in those patients with Crohn's disease than in those with ulcerative colitis (p<0.001). The finding of a subpopulation of cells that simultaneously showed irregular nuclei and B cell markers, such as functional surface IgM, in patients with IBD suggests that an unusual subgroup of B cells that correlates with CD15 expression and a diagnosis of Crohn's disease may be observed in the inflammatory process.

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

“…Morphologically, it seemed that the μ chain-positive segments came from B1-like cells. In previous studies [8,9], we have found B1-like cells in normal and inflammatory intestinal tissue, and in polyps. These cells therefore live on intestinal mucosa, and their number may increase during the inflammatory process.…”

“…However, the remaining four of our tumour samples showed the infiltration of IgM-positive cells with irregular nuclei. These cells infiltrated the tissue in a sporadic manner and were often fragmented (which complicates their additional characterisation), but their microscopic appearance is very particular and identified the same cells previously observed in 35.7% of an IBD population [9]. The cells had lost their structural integrity, but there was no membrane remodelling.…”

“…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]. The aim of this study was to evaluate the distribution of μ chains and CD15+ receptors in biopsy specimens of pre-malignant polyps and adenocarcinomas in order to identify marker distribution in a tumoral context.…”

Identification of molecular subgroups of ulcerative colitis by gene expression profile

“…The hematopoietic cell lineage is the foremost approach leading to UC in ammation. Lineage initiation and lineage transformation of transcription factors can induce lineage transformation of committed cells (Defendenti C et al,2012). Clearing these cells from the circulatory system can enhance the e cacy of drugs and promote disease treatment (Sáez-González E et al,2017).…”

Immunoglobulin M Distribution and Modular Peptide Interactions in the Stroma of Human Colorectal Adenomas and Adenocarcinomas

“…Lymphocytes with a low cytoplasmic/nuclear ratio are found in ulcerative colitis [32] and associated with modified Th2 cytokines [33], whereas IPCs with irregular nuclei are prevalent in Crohn's disease [34] and associated with Th1/Th17 cytokines. In the case of tumors, this dualism recalls tumor-associated macrophages (TAMs).…”