Monday, November 20, 2006

Mouse Lupus prevented with FcgRIIB

drj writes "Mice from some lupus-prone strains make less of an inhibitory antibody receptor (FcgRIIB). Here, mice from these strains were given bone marrow cells that express more FcgRIIB. They lived longer, did not develop as many autoantibodies, and did not develop kidney inflammation (glomerularnephritis). In these experiments, the bone marrow cells from mice representing 3 different lupus models (NZM, BXSB, and B6 FcgRIIB-knockout) were infected (transduced) with retroviruses encoding FcgRIIB. Only about 40% of the B cells made FcgRIIB and the actual increase in expression was "modest" (~43% on B cells; on knockout B cells the increase was presumably qualitative). FcgRIIB may prevent lupus by limiting the development of autoantibodies. Human variations (polymorphisms) that predispose to lupus have been identified in FcgRIIA and FcgRIIIA (review), suggesting a role in human disease. It remains to be seen whether in addition to preventing the onset, retroviral transduction could cure lupus (gene therapy)."
PubMed McGaha et al., Science 307:590-593, Jan. 2005 "Restoration of Tolerance in Lupus by Targeted Inhibitory Receptor Expression".

1 comment:

Reuel said...


FcgRIIB-deficient mice from the B6 (C57BL/6) strain develop lupus but the same knockout in the BALB/c strain do not []. This is presumably due to epistastis [], a fancy name for one gene masking the effect of another. The Ravetch lab attributes epistasis in BALB/c to the immunoglobulin light chain genes, which undergo receptor editing to 'censor' or 'silence' autoreactive combinations of light and heavy chains. Unfortunately, these experiments were performed only with transgenic IgH B6 [] mice, not BALB/c, except for a table reporting the presence (+/-) of autoantibodies. B6 and BALB differences in T helper cell responses were reported nearly a decade ago, with B6 biased toward Th1 responses and BALB/c biased toward Th2 [], attributable to (e.g.) differences in TLR4 signaling [], perhaps mediated through differences in IL-12 production [].

Isn't it likely that these diffences
contribute to the onset of autoimmunity in FcgRII-KO animals?