1 Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands; Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp and Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium. Electronic address: firstname.lastname@example.org.
2 Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
3 Department of Biology, Gilead Sciences, Foster City, United States of America.
BACKGROUND AND AIMS:
Little is known on the frequency, phenotype and function of hepatitis B virus-specific B cells during chronic infection. Here we study hepatitis B core (HBcAg) and surface (HBsAg) antigen-specific B cells in different clinical phases of a chronic HBV infection.
We included 118 treatment naïve and 34 nucleos(t)ide analogue-treated chronic HBV patients and 23 healthy HBsAg-vaccinated controls. Global and HBV-specific B lymphocytes were examined by FACS using fluorescently labeled HBsAg and HBcAg as baits. Functional HBV-specific B cell responses were quantified in B cell ELISPOT assays. Anti-HBs and anti-HBc antibodies were measured in serum and in ELISPOT supernatant by ELISA.
Higher HBcAg-directed B cell responses were found in HBV clinical phases with elevated as compared to low serum ALT levels, irrespective of the HBeAg-status. In contrast, HBsAg-directed responses were lower and did not significantly fluctuate. In individual patients a mean 17.8-fold more circulating B cells target HBcAg than HBsAg baits. These HBcAg-specific B-cells present a classical memory B cell profile and have slightly higher CD69 expression levels compared to global memory B cells. Viral suppression and ALT normalization upon treatment led to a numeric and functional reduction of HBcAg-specific B cells responses, accompanied with progressive decreases in serum HBcAbs.
HBcAg-specific memory B cells present a classical memory B cell phenotype, vary in number and function throughout HBV's natural history and are significantly reduced during antiviral treatment.