The FcμR is broadly expressed on granulocytes, antigen presenting cells, and regulatory T cells and is highly expressed on B cells. In humans, disrupted expression of FcμR is linked to B cell malignancies.
Global deletions of FcμR in mice demonstrated altered cellular activation of antigen presenting cells and levels of serum natural and autoantibodies. However, the contribution of B cell specific FcμR to autoantibody production and B cell homeostasis is not well understood.
Nguyen et al. demonstrated that FcμR is highly expressed on splenic marginal zone (MZ) and B-1 B cells as well as on immature B cells in the bone marrow.
Confocal microscopy further demonstrated that FcμR colocalized with the trans-Golgi network (TGN), where IgM undergoes post-translational modification before being exported to the cell surface.
Mice were generated in which FcμR was conditionally deleted in B cells (FcμR flx/flxCD19-Cre). These allotype-marked B cells were adoptively transferred to reveal that FcμR binds serum IgM.
Proximal ligation assay demonstrated FcμR interacts with IgM in the TGN of immature, but not mature, B cells.
FcμR also constrained expression of the IgM BCR.
Further, FcμR enhanced tonic BCR signaling.
FcμR flx/flxCD19-Cre mice have increased levels of serum IgM, but not IgA or IgG, and increased frequencies of IgM and IgG-specific antibody secreting cells.
FcμR flx/flxCD19-Cre mice also have increased levels of IgG, but not IgM, autoantibodies to double-stranded DNA and increased frequencies of splenic germinal center B cells.
FcμR flx/flxCD19-Cre mice had increased frequencies of B-1a cells in their spleen, but not peritoneal cavity, which greatly contributed to levels of serum IgM.
Last, FcμR regulated cell cycling and survival of B cells.
Overall, FcμR directly restricts the transport of IgM BCR to the surface of developing B cells, regulates tonic BCR signaling.