Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium.
We previously isolated cDNA clones from a human monocyte library that encoded one member of a family of low-affinity surface receptors for the Fc domain of IgG (hFcRII-A). To investigate possible structural and functional heterogeneity among these receptors, we have now isolated two additional cDNAs (hFcRII-B and hFcRII-C) from a human placental library, placenta being a good source of FcR-bearing macrophages and epithelial cells. Three cDNAs encoded related but distinct transmembrane glycoproteins containing two immunoglobulin-like domains; however, transfected cells produced receptors that were indistinguishable on the basis of ligand binding or reactivity with anti-hFcRII monoclonal antibodies. The sequences of hFcRII-A and -B were most closely related and were identical except for several amino acid substitutions and one small internal deletion. While the ectodomain of hFcRII-C was identical to hFcRII-B, its cytoplasmic tail was unrelated but highly homologous to the corresponding domain of the receptor isoform (mFcRII-B2) found in murine macrophages. Thus, human FcRII may be derived from at least two alternatively spliced genes. Northern blots revealed little difference in the pattern of expression of hFcRII isoforms among various myeloid and lymphoid cells or cell lines. However, the blots--as well as in situ hybridization and immunohistochemistry--demonstrated that hFcRII-C (along with a second monocyte marker, the c-fms encoded CSF-1 receptor) was expressed in placental syncytiotrophoblasts. Since syncytiotrophoblasts comprise the IgG-transporting epithelium of the placental villus, these findings suggest that FcR found in the immune system and in certain epithelia may be structurally or functionally related.
Stuart
S G
SG
Department of Molecular and Cell Biology, Triton Biosciences, Inc., Alameda, CA 94501.
Simister
N E
NE
Clarkson
S B
SB
Kacinski
B M
BM
Shapiro
M
M
Mellman
I
I
D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D001483:Base Sequence; D001692:Biological Transport; D002460:Cell Line; D004247:DNA / Q000302:isolation & purification; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008969:Molecular Sequence Data; D011257:Pregnancy Proteins / Q000378:metabolism*; D011961:Receptors, Fc / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D017452:Receptors, IgG; D012689:Sequence Homology, Nucleic Acid; D014327:Trophoblasts / Q000378:metabolism
D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011257:Pregnancy Proteins; D011961:Receptors, Fc; D017452:Receptors, IgG; D004247:DNA