Sorted B cell transcriptomes point towards actively regulated B cell responses during ongoing chronic hepatitis B infections
Stijn Van Hees 1 , Bart Cuypers 2 , Stefan Bourgeois 3 , Zwier M A Groothuismink 4 , Pieter Meysman 5 , Pieter Van der Vlies 6 , Rob de Knegt 4 , Luisa Vonghia 1 , Peter Michielsen 1 , Sven Francque 1 , Kris Laukens 5 , Andre Boonstra 4 , Thomas Vanwolleghem 7
Affiliations
Affiliations
1
Department of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium; Laboratory of Experimental Medicine and Paediatrics, Antwerp University, Universiteitsplein 1, 2610 Antwerp, Belgium.
2
Department of Biomedical Sciences, Institute of Tropical Medicine, Kronenburgstraat 43, 2000 Antwerp, Belgium; Department of Mathematics and Computer Science, University of Antwerp, Middelheimlaan 1, 2020 Antwerp, Belgium.
3
Department of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium; Department of Gastroenterology and Hepatology, ZNA Stuivenberg, Antwerp, Belgium.
4
Department of Gastroenterology and Hepatology, Erasmus Medical Center Rotterdam, the Netherlands.
5
Department of Mathematics and Computer Science, University of Antwerp, Middelheimlaan 1, 2020 Antwerp, Belgium.
6
Department of Genetics, University Medical Center Groningen, the Netherlands.
7
Department of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium; Laboratory of Experimental Medicine and Paediatrics, Antwerp University, Universiteitsplein 1, 2610 Antwerp, Belgium; Department of Gastroenterology and Hepatology, Erasmus Medical Center Rotterdam, the Netherlands. Electronic address: [email protected].
PMID: 33548734 DOI: 10.1016/j.cellimm.2021.104283
Abstract
The natural course of chronic hepatitis B virus (HBV) infections follows distinct clinical disease phases, characterized by fluctuating levels of serum HBV DNA and ALT. The immune cells and their features that govern these clinical disease transitions remain unknown. In the current study, we performed RNA sequencing on purified B cells from blood (n = 42) and liver (n = 10) of healthy controls and chronic HBV patients. We found distinct gene expression profiles between healthy controls and chronic HBV patients, as evidenced by 190 differentially expressed genes (DEG), but also between the clinical phenotypes of a chronic HBV infection (17-110 DEG between each phase). Numerous immune pathways, including the B cell receptor pathway were upregulated in liver B cells when compared to peripheral B cells. Further investigation of the detected DEG suggested an activation of B cells during HBeAg seroconversion and an active regulation of B cell signalling in the liver.