ROLE OF B-CELLS IN ANTIGEN PRESENTATION OF THE HEPATITIS-B CORE

The hepatitis B virus (HBV) nucleocapsid or core antigen (HBcAg) is ex tremely immunogenic during infection and after immunization, For examp le, during many chronic infections, HBcAg is the only antigen capable of eliciting an immune response, and nanogram amounts of HBcAg elicit antibody production in mice, Recent structural analysis has revealed a number of characteristics that may help explain this potent immunogen icity, Our analysis of how the HBcAg is presented to the immune system revealed that the HBcAg binds to specific membrane Ig (mig) antigen r eceptors on a high frequency of resting, murine B cells sufficiently t o induce B7.1 and B7.2 costimulatory molecules, This enables HBcAg-spe cific B cells from unprimed mice to take up, process, and present HBcA g to naive Th cells in vivo and to T cell hybridomas in vitro approxim ately 10(5) times more efficiently than classical macrophage or dendri tic antigen-presenting cells (APC), These results reveal a structure-f unction relation for the HBcAg, confirm that B cells can function as p rimary APC, explain the enhanced immunogenicity of HBcAg, and may have relevance for the induction and/or maintenance of chronic HBV infecti on.