8 Immunology of gastrointestinal lymphoma

Abstract

Experimental work showing that IgA plasma cell precursors activated in gut associated lymphoid tissue (GALT) of rats and sheep migrate to the lamina propria of the gut via the regional lymphatics, mesenteric lymph node and blood, has been supported by immunohistochemical studies. In rats, immunoblasts with cytoplasmic IgA are present in the Peyer's patches in association with the high endothelial venules which is probably an important, though not the only, site of extravasation into the gut, whereas cells with cytoplasmic IgA are rarely observed in the dome regions of Peyer's patches. Immunohistochemical studies of human Peyer's patches have revealed differences between the distribution of cells with cytoplasmic IgA in man compared to rats. In man, immunoblasts with cytoplasmic IgA are not concentrated in the zone of cells containing the high endothelial venules, whereas they are present in the dome regions of the Peyer's patches. The following questions arise: Do precursors of IgA plasma cells activated in human GALT migrate to the lamina propria via the blood, but extravasate predominantly via the capillary network, rather than the high endothelial venules? or do IgA plasma cell precursors ‘mature’ in situ in the Peyer's patches of man and subsequently migrate laterally to seed the lamina propria? Three lines of evidence from studies of primary B cell lymphomas of GALT support the latter hypothesis: 1) Primary B cell lymphomas of the gut remain localized to GALT for long periods of time; 2) Histological studies of the lymphoid tissue in these lymphomas have shown a gradation of cell types, from the muscularis mucosae towards the mucosal epithelium, which strongly suggests that plasma cells develop in situ in the gut from the adjacent layers of cells; 3) Preliminary studies of DNA extracted from the blood-borne cells from patients with GALT-derived B cell lymphoma have failed to demonstrate the presence of clonal gene rearrangements. Normal and malignant human GALT contains a perifollicular population of B cells with centrocyte-like morphology which lack surface IgD. No direct equivalent can be detected in rodent Peyer's patches. Their quiescent nature and distribution in malignant GALT suggests that they are follicle centre cell-derived and precursors of immunoblasts and plasma cells. As such they may be memory B cells. Their association with epithelium is a consistent feature of normal and malignant GALT which is of unknown but undoubted significance. The function of intraepithelial T cells is still unknown. Malignant T cells in MHI may be derived from intraepithelial T cells. Further studies of these malignant T cells which are now in progress may enable a new approach to the investigation of human intraepithelial lymphocytes.