Boonstra, Andre

Groothuismink, Zwier M.A.

Hung, Magdeleine

Kreefft, Kim

Novikov, Nikolai

Vanwolleghem, Thomas

Abstract: 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 na\uefve 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\u2019s natural history and are significantly reduced during antiviral treatment

Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV

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