Selective regulation of autoreactive B cells by FcgammaRIIB

FcgammaRIIB is an inhibitory receptor which plays a role in limiting B cell and DC activation. Since FcgammaRIIB is known to dampen the signaling strength of the BCR, we wished to determine the impact of FcgammaRIIB on the regulation of BCRs which differ in their affinity for DNA. For these studies, FcgammaRIIB deficient BALB/c mice were bred with mice expressing the transgene-encoded H chain of the R4A anti-DNA antibody which gives rise to BCRs which express high, low or no affinity for DNA. The deletion of FcgammaRIIB in R4A BALB/c mice led to an alteration in the B cell repertoire, allowing for the expansion and activation of high affinity DNA-reactive B cells. By 6-8 months of age, R4A x FcgammaRIIB-/- BALB/c mice spontaneously developed anti-DNA antibody titers. These mice also displayed an induction of IFN-inducible genes and an elevation in levels of the B cell survival factor, BAFF. These data demonstrate that FcgammaRIIB preferentially limits activation of high affinity autoreactive B cells and can influence the activation of DC through an immune complex-mediated mechanism.