Anti-FCGR2B monoclonal antibody, clone 7D5 [APC]

Data suggests that modulation of Fc gamma RIIB expression represents a significant risk factor for the development of autoimmunity. In this study, we investigated this notion in mice that possess genetics permissible for the development of autoimmunity. To this end, Mrl-MpJ Fcgr2b-/- mice were monitored for the development of autoreactivity. We found that Fc gamma RIIB deficiency led to chronic B cell activation associated with increased germinal center and plasma cell accumulation in the spleen. Likewise, Mrl-MpJ Fcgr2b-/- mice exhibited significant serum IgG reactivity against DNA. We further analyzed the IgG isotype contribution to the anti-dsDNA response and found increases in all subtypes with the exception of IgG3. In particular, we found large increases in IgG1 and IgG2b autoreactivity correlating with significant increases in immune complex deposition and kidney pathology. Finally, we found dendritic cells derived from Mrl-MpJ Fcgr2b-/- mice greatly increased IL-12 expression upon coincubation with apoptotic thymocytes compared with wild-type controls. The results indicate that Fc gamma RIIB is an important regulator of peripheral tolerance and attenuation of the inhibitory signal it provides enhances autoimmune disease on susceptible backgrounds. Additionally, the data indicates Fc gamma RIIB function has a significant impact on APC activity, suggesting a prominent role in dendritic cell activity in response to interaction with particulate autoantigens.

Cervicovaginal epithelium plays a critical role in determining the outcome of virus transmission in the female reproductive tract (FRT) by initiating or suppressing transmission-facilitating mucosal immune responses in naive and SIVmac239 Delta nef-vaccinated animals, respectively. In this study, we examined the very early responses of cervical epithelium within 24 h after vaginal exposure to SIV in naive and SIVmac239 Delta nef-vaccinated rhesus macaques. Using both ex vivo and in vivo experimental systems, we found that vaginal exposure to SIV rapidly induces a broad spectrum of pro-inflammatory responses in the epithelium associated with a reciprocal regulation of NF-kB and glucocorticoid receptor (GR) signaling pathways. Conversely, maintenance of high-level GR expression and suppression of NF-kB expression in the epithelium were associated with an immunologically quiescent state in the FRT mucosa and protection against vaginal challenge in SIVmac239Dnef-vaccinated animals. We show that the immunologically quiescent state is induced by FCGR2B-immune complexes interactions that modify the reciprocal regulation of NF-kB and GR signaling pathways. Our results suggest that targeting the balance of NF-kB and GR signaling in early cervicovaginal epithelium responses could moderate mucosal inflammation and target cell availability after vaginal infection, thereby providing a complementary approach to current prevention strategies.