Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium.

Abstract

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.

Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

“…In particular, Ick is expressed in T-lymphoid cells and natural killer cells and to a lesser degree in some B cells (8), blk is expressed in B-lymphoid cells (20), fgr is expressed in normal monocytic cells and granulocytes (37), and hck is expressed in monocytes and granulocytes and at low levels in some B cells (41 in a signal transduction pathway common to myeloid cells and B-lymphoid cells. In this regard, it is interesting to note that several membrane molecules are expressed in a similar pattern on hematopoietic cells, including the receptors for complement components and the Fc portion of immunoglobulin molecules (31,33). Cross-linking of these cell surface molecules induces rapid tyrosine phosphorylation of several cellular proteins (31) protease digestion patterns were very similar for all of the proteins, demonstrating their identity and indicating that phosphorylation occurred on comparable sites in immunoprecipitates.…”

“…In this regard, it is interesting to note that several membrane molecules are expressed in a similar pattern on hematopoietic cells, including the receptors for complement components and the Fc portion of immunoglobulin molecules (31,33). Cross-linking of these cell surface molecules induces rapid tyrosine phosphorylation of several cellular proteins (31) protease digestion patterns were very similar for all of the proteins, demonstrating their identity and indicating that phosphorylation occurred on comparable sites in immunoprecipitates. The one exception was a small fragment that was seen only in digests of the 56-kDa lynA protein.…”

Expression of placental alkaline phosphatase does not correlate with IgG binding, internalization and transcytosis

“…However, in the third trimester, the number of cytotrophoblasts is greatly reduced and the feto-maternal barrier then consists of the syncytiotrophoblast and the fetal capillary endothelium [5]. Although Fc receptors have been localized in syncytiotrophoblast as well as in fetal endothelial cells [4,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]], the precise mechanism by which IgG crosses the term placenta is not fully understood.…”

The polymeric immunoglobulin receptor. A model protein to study transcytosis.

“…Examples of transcytosis include the transport ofinsulin and serum albumin across endothelia (6), epidermal growth factor across kidney epithelia (7), and intestinal epithelia (8), and transferrin across capillaries in the brain (3). The beststudied examples of transcytosis are the transport of immunoglobulins that occurs in at least three situations in mammals: transport of IgG across the intestinal epithelium in newborn rats (9), transport of IgG across the human placenta (10), and transport of IgA and IgM across various mucosae (1 1).…”