The interaction between immune responses and hepatitis B virus (HBV) is coordinated between innate and adaptive immunity. Anti-HBs antibodies protect the host by blocking the binding ability of HBV. Anti-HBc antibodies are detected with persistent HBV infection. The presence of anti-HBe antibodies is often associated with recovery from active diseases and is clinically used as a benchmark to assess response to treatment. Our studies have revealed that the anti-HBV immunoglobulins secreted are different in subclass patterns in different HBV infection status populations. These revelations may help to understand HBV escape and persistent infection and to develop strategies for prevention and therapeutic management of HBV infection.