Molecular characterization of the dimer formation of Fcα/μ receptor (CD351)

Abstract

Fcα/μR (CD351) is an Fc receptor for both IgA and IgM and forms an atypical dimer that is resistant to reduction by 2-mercaptoethanol or boiling. We previously demonstrated that the cytoplasmic portion of Fcα/μR is required for dimer formation and for its efficient cell-surface expression. However, the biochemical nature of these phenomena has not been determined. By using a BW5147 mouse cell line expressing deletion mutants of the cytoplasmic region of Fcα/μR, we found that the region spanning amino acids 504-523 was required for efficient cell-surface expression, whereas the region spanning amino acids 481-490 was required for dimmer formation. Immunoblotting analyses of transfectants simultaneously expressing Flag-tagged Fcα/μR and hemagglutinin-tagged Fcα/μR suggested that Fcα/μR does not form homodimers. Instead, our data suggest that Fcα/μR forms heterodimers with an as-yet-unknown molecule with a molecular weight of 60-70 kDa.

Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling

“…Feamr gene is located near the clusters for IgG FcRs on chromosome 1 (refs 15 , 17 , 18 ). The cytoplasmic region of Fcα/μR is required for an atypical dimer formation 19 20 . Fcα/μR is preferentially expressed on follicular dendritic cells in the lymphoid organs 21 and suppresses T -independent antigen retention by follicular dendritic cells, leading to the downregulation of germinal centre formation and humoral immune responses, including antibody production, affinity maturation and memory B-cell generation, against T -independent antigens 21 .…”

Immune regulation by Fcα/μ receptor (CD351) on marginal zone B cells and follicular dendritic cells

“…Surprisingly, immunoblotting analyses of transfectants simultaneously expressing two types of Fcα/μR tagged with Flag and HA (hemagglutinin) at the N‐terminus demonstrated that Flag‐tagged Fcα/μR was not coimmunoprecipitated with HA‐tagged Fcα/μR. Conversely, an anti‐HA antibody immunoprecipitated HA‐tagged Fcα/μR alone, but not Flag‐tagged Fcα/μR . These results suggest that Fcα/μR does not form homodimers.…”

“…In contrast to BW5147 transfectants expressing WT Fcα/μR, which shows both monomeric and dimeric formations, BW5147 cells transfected with mutated Fcamr cDNA encoding Fcα/μR lacking the cytoplasmic portion expressed only monomeric Fcα/μR protein , suggesting that the cytoplasmic portion is required for dimer formation of Fcα/μR and efficient cell surface expression of Fcα/μR. Further analyses demonstrated that the regions spanning 481–490 and 504–523 amino acids are essential for dimer formation and efficient cell surface expression of Fcα/μR, respectively ( Fig. ).…”

Involvement of Fcα/μR (CD351) in autoantibody production

“…FcR forms an atypical dimer, for which the cytoplasmic region of FcR is required (Cho et al, 2010;Takagaki et al, 2013). FcR is moderately expressed on B cells and macrophages (Sakamoto et al, 2001;Shibuya et al, 2000), and most strongly on follicular dendritic cells (FDCs) (Cho et al, 2006;Honda et al, 2009;Usui et al, 2012), which is involved in germinal center (GC) formation (Chaplin and Zindl, 2006;Park and Choi, 2005).…”