A NOVEL ROLE FOR B-CELLS IN EARLY PROTECTIVE IMMUNITY TO AN INTRACELLULAR PATHOGEN, FRANCISELLA-TULARENSIS STRAIN LVS

Normal BALB/cByJ mice given a sublethal infection of Francisella tular ensis strain LVS survived 10(6) LD(50)s Of lethal challenge given only 3 days later. Here, we determine the cell types responsible for this very strong early protective immunity. Early protection is observed in athymic nu/nu mice but not fully immunodeficient scid mice, implicati ng a lymphocyte in this response. Using scid mice that are reconstitut ed with various purified cell subpopulations, as well as mice with gen etically targeted disruptions in lymphocyte subpopulations (knockout m ice), we demonstrate that strong early protection is highly dependent on B cells. This protective mechanism, which limits bacterial growth i n the organs of the reticuloendothelial system very quickly after infe ction, requires IFN-gamma but is unlikely to involve specific Ab.