| First Author | Fukuyama H | Year | 2005 |
| Journal | Nat Immunol | Volume | 6 |
| Issue | 1 | Pages | 99-106 |
| PubMed ID | 15592473 | Mgi Jnum | J:94871 |
| Mgi Id | MGI:3521629 | Doi | 10.1038/ni1151 |
| Citation | Fukuyama H, et al. (2005) The inhibitory Fcgamma receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells. Nat Immunol 6(1):99-106 |
| abstractText | Deletion of the gene encoding the Fc immunoglobulin G receptor IIB (FcgammaRIIB) results in a fulminant, lupus-like disease in C57BL/6 but not BALB/c mice. Here we have investigated this strain-specific, epistatic loss of tolerance using gene-targeted immunoglobulin variable heavy-chain (V(H)) alleles 3H9 or 56R, which encode DNA-specific heavy chains, expressed on the C57BL/6 or BALB/c background. The combination of C57BL/6 and V(H) 56R (B6.56R) resulted in a loss of tolerance; hybridoma and single-cell analysis indicated an FcgammaRIIB-independent difference in immunoglobulin light-chain usage, consistent with an alteration in receptor editing. FcgammaRIIB deficiency resulted in an increase in immunoglobulin G (IgG) antibodies to DNA in the serum, an increased frequency of anti-DNA-reactive IgG(+) B cells with a plasma cell phenotype and immune complex deposition in the glomeruli and renal disease in B6.56R mice. Thus, FcgammaRIIB provides a distal peripheral checkpoint to limit the accumulation of autoreactive plasma cells, thereby maintaining tolerance. |
