乙型肝炎病毒（HBV）感染时，乙肝表面抗体（抗-HBs）的出现通常预示着清除乙肝病毒。但一部分慢性HBV感染者血清学表现为乙肝表面抗原（HBsAg）与抗-HBs同时阳性，此类患者病毒免疫清除期较长，其抗-HBs无法清除病毒的机制不明。我们前期研究显示，抗-HBs阳性的患者HBsAg与抗-HBs阴性的对照组相比不存在新的变异位点，变异率无明显差异，提示HBsAg变异不是出现HBsAg和抗-HBs双阳性的主要原因，因此我们提出抗-HBs的异常导致机体无法清除乙肝病毒。本项目采用单个B细胞克隆技术、生物信息学分析、抗-HBs中和实验、重叠肽及丙氨酸扫描突变等实验方法，建立抗-HBs信息库，进行抗-HBs抗体序列、结构和功能研究，探索抗-HBs异常导致HBsAg（+）/抗-HBs（+）慢性乙型肝炎病毒感染者无法清除乙肝病毒的可能机制，为慢性乙型病毒性肝炎的免疫机制研究提供思路。

During hepatitis B virus (HBV) infection, virus clearance is characterized by the emergence of anti-HBs and the disappearance of the HBsAg in serological profiles. However, the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection has been often reported. The mechanism underlying the emergence of anti-HBs in these patients remains unclear. Our previous study showed no additional HBsAg variants, higher or lower mutation rates could be found among patients with positive anti-HBs, thereby anti-HBs dysfunction may be the reason why HBsAg and virus exist in these patients. Using single B cell cloning technologies, bioinformatic analysis, neutralization tests, et al, we are supposed to establish anti-HBs databases of patients with coexisting HBsAg and anti-HBs, containing sequences and conformations. The in-depth functional study of anti-HBs in patients during chronic HBV infection may uncover the mechanism of the coexistence of HBsAg and anti-HBs, and contribute to the explore of immunologic mechanism during chronic hepatitis B.