B cells regulate luminal bile acid composition in the small intestine

Abstract

Abstract Recent studies have demonstrated that bile acids (BA) influence immune cell homeostasis in the gut. However, whether and how, the host immune response can influence BA biochemistry is unknown. This is an important question to answer because small shifts in BA composition in the gut can have significant pathophysiological consequences. Previously, we have demonstrated that CD19 −/−mice, which have a defect in B cell activation and consequently an aberrant humoral immune response, develop a small intestine (SI) enteropathy that is associated with abnormal luminal BA composition. However, CD19 −/−mice are not B-cell-deficient and present with multiple aberrant immune phenotypes. Here, we used B cell-deficient JHminus;/minus; mice to more effectively define this interaction. Results of our experiments provide three key observations. First, J H−/−mice develop altered SI BA pools compared to their WT littermates. Second, adoptive transfer of WT B cells into neonatal J H−/−mice led to the development of normal BA pools and rescued mice from SI enteropathy. Third, adoptive transfer of B cells incapable of secreting IgA into neonatal J H−/−mice failed to restore normal bile acid composition and only moderately protected animals from developing SI enteropathy. Collectively, the results of our experiments clearly demonstrate that B cells regulate bile acid composition in the SI and that the synthesis of mucosal IgA may be particularly important for driving this effect.