Background & Aims: Little is known about the frequency, phenotype and function of HBV-specific B cells during chronic infection. Here we study HBcAg and HBsAg-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 patients with chronic HBV 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 vs. low serum alanine aminotransferase (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 cell responses, accompanied by progressive decreases in serum anti-HBc antibodies. 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. Lay summary: In recent years, studies examining the role of B cells during chronic hepatitis B virus infection have regained interest. We show that circulating B cells more often target the hepatitis B core antigen than the hepatitis surface antigen. Moreover, these hepatitis B core-specific B cells associate with the natural history of chronic HBV, and their responses decline during effective antiviral treatment.

Additional Metadata
Keywords B cell, ELISPOT, Hepatitis B core antigen, Hepatitis B virus
Persistent URL dx.doi.org/10.1016/j.jhep.2020.01.024, hdl.handle.net/1765/126171
Journal Journal of Hepatology
Citation
Vanwolleghem, T, Groothuismink, Z.M.A, Kreefft, K, Hung, M. (Magdeleine), Novikov, N. (Nikolai), & Boonstra, P.A. (2020). Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV. Journal of Hepatology. doi:10.1016/j.jhep.2020.01.024