However, 6- and 10-month-old FcγRIIB<sup>-/-</sup> males that developed an SLE-like phenotype were osteopenic and FcγRIIB deletion resulted in decreased cancellous bone volume.
FcγRIIb-I232T is a hypofunctional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells.
CD19<sup>Cre</sup><i>Yaa</i> mice developed milder lupus than B6.FcγRIIb<sup>-/-</sup><i>Yaa</i> mice, indicating that FcγRIIb deficiency on B cells is not sufficient for the development of severe disease.
We investigated the influence of spontaneous gut leakage upon polymicrobial sepsis in a lupus model with Fc gamma receptor IIb-deficient (FcGRIIb-/-) mice aged 8 and 40 weeks, as representing asymptomatic and symptomatic lupus, respectively.
Indeed, recent epidemiological studies revealed that a non-synonymous single nucleotide polymorphism (rs1050501) within the TM domain of FcγRIIB, responsible for the I232T substitution, is associated with the susceptibility to systemic lupus erythematosus (SLE).
The inflammation intensity in the liver decreased with IgG depletion and the lupus IgG-induced liver inflammation in FcγRIII-deficient mice was comparatively low; while, inflammation was increased in FcγRIIb-deficient mice.
Recently, among other mutations, rare null-alleles for the deoxyribonuclease 1 like 3 (<i>DNASE1L3</i>) and the Fc gamma receptor IIB (<i>FCGR2B</i>) have been described in SLE patients and genetic mouse models.
Because mice deficient in either Sirt1 or FcγRIIB develop lupus-like diseases, we investigated whether resveratrol can alleviate lupus through FcγRIIB.
In the present study, we have investigated nephritis development and progression in FcγRIIB-/-yaa mice to find shared features with NZB/NZW F1 lupus prone mice and human disease.
Our study demonstrated an association of FcγRIIB polymorphisms with SLE and lupus nephritis and a lack of association of FcγRIIA polymorphisms with SLE in the Egyptian patients.
This inhibitory function of FcγRIIB in impairing the spatial-temporal colocalization of BCR and CD19 microclusters in the B cell immunological synapse may help explain the hyper-reactive features of systemic lupus erythematosus patient B cells in reported studies.
A single nucleotide polymorphism in human FcγRIIB (rs1050501) results in profound receptor dysfunction and is associated with systemic lupus erythematosus.
Selective silencing of double-stranded DNA-specific B cells in animals with spontaneous lupus has been achieved previously by the administration of a chimeric antibody molecule that cross-links their DNA-reactive B cell immunoglobulin receptors with inhibitory FcγIIb (CD32) receptors.
We conclude that FCGR3B deletion juxtaposes the 5'-regulatory sequences of FCGR2C with the coding sequence of FCGR2B, creating a chimeric gene that results in an ectopic accumulation of FcγRIIb on NK cells and provides an explanation for SLE risk associated with reduced FCGR3B gene copy number.
Given that the murine lupus susceptibility locus Nba2 includes the IFN-regulated genes Ifi202 (encoding for the p202 protein), Aim2 (encoding for the Aim2 protein), and Fcgr2b (encoding for the FcγRIIB receptor), we investigated whether the IRF5/Blimp-1 axis could regulate the expression of these genes.
Interestingly, recent studies involving the generation of Nba2 subcongenic mouse lines and generation of mice deficient for the Fcgr2b or Aim2 gene within the interval have provided evidence that epistatic interactions among the Nba2 genes contribute to increased lupus susceptibility.
Immune complex-mediated co-ligation of the BCR with FcγRIIB results in homeostatic apoptosis of B cells involving Fas signalling that is defective in the MRL/Lpr model of systemic lupus erythematosus.
We previously demonstrated significant association of the polymorphism of the CD72 gene with susceptibility to human systemic lupus erythematosus (SLE) in individuals carrying a SLE-susceptible FCGR2B genotype (FCGR2B-232Thr/Thr).