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Fc gamma receptor IIB (Fc γ RIIB) is the only Fc gamma receptor (Fc γ R) which negatively regulates the immune response, when engaged by antigen- (Ag-) antibody (Ab) complexes. Thus, the generation of Ag-specific IgG in response to infection or immunization has the potential to downmodulate immune protection against infection. Therefore, we sought to determine the impact of Fc γ RIIB on immune protection against  Francisella tularensis  ( Ft ), a Category A biothreat agent. We utilized inactivated  Ft  (i Ft ) as an immunogen. Naïve and i Ft -immunized Fc γ RIIB knockout (KO) or wildtype (WT) mice were challenged with  Ft -live vaccine strain (LVS). While no significant difference in survival between naïve Fc γ RIIB KO versus WT mice was observed, i Ft -immunized Fc γ RIIB KO mice were significantly better protected than i Ft -immunized WT mice.  Ft -specific IgA in serum and bronchial alveolar lavage, as well as IFN- γ , IL-10, and TNF- α  production by splenocytes harvested from i Ft -immunized Fc γ RIIB KO, were also significantly elevated. In addition, i Ft -immunized Fc γ RIIB KO mice exhibited a reduction in proinflammatory cytokine levels  in vivo  at 5 days after challenge, which correlates with increased survival following  Ft -LVS challenge in published studies. Thus, these studies demonstrate for the first time the ability of Fc γ RIIB to regulate vaccine-induced IgA production and downmodulate immunity and protection. The immune mechanisms behind the above observations and their potential impact on vaccine development are discussed.

journal of immunology research

Downmodulation of Vaccine-Induced Immunity and Protection against the Intracellular Bacterium<i>Francisella tularensis</i>by the Inhibitory Receptor Fc<i>γ</i>RIIB

Downmodulation of Vaccine-Induced Immunity and Protection against the Intracellular BacteriumFrancisella tularensisby the Inhibitory Receptor FcγRIIB