Protective long-term antibody memory by antigen-driven and T help-dependent differentiation of long-lived memory B cells to short-lived plasma cells independent of secondary lymphoid organs

Memory is a hallmark of immunity. Memory carried by antibodies is largely r esponsible for protection against reinfection with most known acutely letha l infectious agents and is the basis for most clinically successful vaccine s, However, the nature of long-term B cell and antibody memory is still unc lear. B cell memory was studied here after infection of mice with the rabie s-like cytopathic vesicular stomatitis virus, the noncytopathic lymphocytic choriomeningitis virus (Armstrong and WE), and after immunization with var ious inert viral antigens inducing naive B cells to differentiate either to plasma cells or memory B cells in germinal centers of secondary lymphoid o rgans. The results show that in contrast to very low background levels agai nst internal viral antigens, no significant neutralizing antibody memory wa s observed in the absence of antigen and suggest that memory B cells (i) ar e long-lived in the absence of antigen, nondividing, and relatively resista nt to irradiation, and (ii) must be stimulated by antigen to differentiate to short-lived antibody-secreting plasma cells, a process that is also effi cient in the bone marrow and always depends on radiosensitive, specific T h elp. Therefore, for vaccines to induce long-term protective antibody titers , they need to repeatedly provide, or continuously maintain, antigen in min imal quantities over a prolonged time period in secondary lymphoid organs o r the bone marrow for sufficient numbers of long-lived memory B cells to ma ture to short-lived plasma cells.