The multi-organ landscape of B cells highlights dysregulated memory B cell responses in Crohn's disease.

Abstract

Crohn's disease (CD) is a prevalent type of inflammatory bowel disease (IBD) with dysregulated antibody responses. However, there is a lack of comprehensive analysis of B cell responses in CD. Here, we collected B cells from the small intestine, colon and blood of CD patients and control subjects. Through the coupled analysis of transcriptome and immunoglobulin (Ig) gene in individual cells, we characterized the cellular composition, transcriptome and Ig clonotype in different B cell subtypes. We observed shared disruptions in plasma cell (PC) responses between different IBD subtypes. We revealed heterogeneity in memory B cells (MBCs) and showed a positive correlation between gut resident-like MBCs and disease severity. Furthermore, our clonotype analysis demonstrated an increased direct differentiation of MBCs into PCs in CD patients. Overall, this study demonstrates significantly altered B cell responses associated with chronic inflammation during CD and highlights the potential role of mucosal MBCs in CD pathogenesis.