Susceptibility to secondary Francisella tularensis live vaccine strain infection in B-cell-deficient mice is associated with neutrophilia but not with defects in specific T-cell-mediated immunity

Previous studies have demonstrated a role for B cells, not associated with antibody production, in protection against lethal secondary infection of mi ce with Francisella tularensis live vaccine strain (LVS). However, the mech anism by which B cells contribute to this protection is not known. To study the specific role of B cells during secondary LVS infection, we developed an in vitro culture system that mimics many of the same characteristics of in vivo infection. Using this culture system, we showed that B cells do not directly control LVS infection but that control of LVS growth is mediated primarily by LVS-primed T cells. Importantly, B cells were not required for the generation of effective memory T cells since LVS-primed, B-cell-defici ent (BKO) mice generated CD4(+) and CD8(+) T cells that controlled LVS infe ction similarly to LVS-primed CD4(+) and CD8(+) T cells from wild-type mice . The control of LVS growth appeared to depend primarily on gamma interfero n and nitric oxide and was similar in wild-type and BKO mice. Rather, the i nability of BKO mice to survive secondary LVS infection was associated with marked neutrophil influx into the spleen very early after challenge. The n eutrophilia was directly associated with B cells, since BKO mice reconstitu ted with naive B cells prior to a secondary challenge with LVS had decrease d bacterial loads and neutrophils in the spleen and survived.