The inhibitory Fcγ receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells

H Fukuyama, F Nimmerjahn, JV Ravetch - Nature immunology, 2005 - nature.com
Nature immunology, 2005nature.com
Deletion of the gene encoding the Fc immunoglobulin G receptor IIB (FcγRIIB) 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 (VH) 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 VH 56R (B6. 56R)
resulted in a loss of tolerance; hybridoma and single-cell analysis indicated an FcγRIIB …
Abstract
Deletion of the gene encoding the Fc immunoglobulin G receptor IIB (FcγRIIB) 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 (VH) 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 VH 56R (B6.56R) resulted in a loss of tolerance; hybridoma and single-cell analysis indicated an FcγRIIB-independent difference in immunoglobulin light-chain usage, consistent with an alteration in receptor editing. FcγRIIB 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, FcγRIIB provides a distal peripheral checkpoint to limit the accumulation of autoreactive plasma cells, thereby maintaining tolerance.
nature.com