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Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV.
Vanwolleghem, Thomas
Groothuismink, Zwier M A
Kreefft, Kim
Hung, Magdeleine
Novikov, Nikolai
Boonstra, Andre
Journal of hepatology 2020 Jul;73(1): 52-61

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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

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