Entering the spotlight: hepatitis B surface antigen-specific B cells

Abstract

Hepatitis B virus-specific (HBV-specific) T cells have been identified as main effector cells in HBV clearance. In contrast, B cells producing neutralizing antibodies against the HBV surface antigen (HBsAg) have been studied in little detail, mainly due to methodical limitations. In this issue of the JCI, two reports use a new technique to specifically detect and characterize HBsAg-specific B cells ex vivo. Indeed, these cells are present, but show phenotypic alterations and impaired function during acute and chronic HBV infection. Thus, HBsAg-specific B cells are a novel attractive target for antiviral strategies toward functional cure of chronic HBV infection.

Figure 1. HBsAg-specific B cells in HBV infection.

(A) Fluorochrome-labeled HBsAg binds to the HBsAg-specific B cell receptor (BCR) of HBsAg-specific B cells, allowing their detection and characterization directly ex vivo. Using this approach, phenotypical as well as functional differences between HBsAg-specific B cells in acute and chronic infection versus resolved infection were identified. (B) In acute and chronic infection, HBsAg-specific B cells are present in similar frequencies compared with their presence in resolved infection; however, they display low expression of CD21 and CD27 (consistent with atypical memory B cells) as well as a high expression of inhibitory receptors, such as PD-1, BTLA, CD22, FcγRIIB, and FcRL5. They also highly express the transcription factor T-bet and are not able to differentiate into anti-HBs–secreting plasma cells. These phenotypical alterations are enriched in the liver. However, they are not restricted to HBsAg-specific B cells, but affect the global B cell compartment of patients with acute or chronic HBV infection.