Enhanced oxidative phosphorylation of IgG plasma cells can contribute to hypoxia in the mucosa of active ulcerative colitis

Abstract

Mucosal hypoxia is detected in the mucosa of ulcerative colitis (UC), however the mechanism and the cause of hypoxia is not fully understood, while a dense infiltration of plasma cells is observed in the inflamed mucosa of UC. When differentiating from a B cell to a plasma cell, the energy metabolism dramatically shifts from glycolysis to oxidative phosphorylation, which results in a large amount of oxygen consumption of the plasma cell. We hypothesized that the plasma cell infiltration into the inflamed mucosa contributes to the mucosal hypoxia in UC in part. We examined the association between mucosal hypoxia and plasma cell infiltration in UC. More IgG plasma cells (but not IgA plasma cells) were distributed, and the nuclear and cell sizes were enlarged in hypoxic mucosa compared to normoxic mucosa in UC. Oxidative phosphorylation signature genes of these IgG plasma cells were markedly upregulated compared to those of other lymphoid cells infiltrating the lamina propria of inflamed mucosa of UC. Enlarged IgG plasma cells, which increase in number in the inflamed mucosa of UC, can be related to the hypoxic state of the inflamed mucosa of UC.

Keywords: Hypoxia; IgG; Plasma cells; Tertiary lymphoid organ; Ulceration; Ulcerative colitis.