ANALYSIS AT THE DNA LEVEL OF HUMAN FC-GAMMA-RII ISOFORMS IN RELATION TO THE POLYMORPHIC BINDING OF MURINE IGG2B TO HUMAN B-CELLS

Three classes of human leucocyte Fc gamma receptors (hFc gamma R) have been identified so far: hFc gamma RI, hFc gamma RII, and hFc gamma RI II. Previous studies have demonstrated that genetically determined dif ferences between individuals exist both with respect to the binding of murine IgG1 (mIgG1) to hFc gamma receptors, and with respect to the b inding of murine IgG2b (mIgG2b). The polymorphism in binding of mIgG1 could be ascribed to hFc gamma RIIA, an isoform of hFc gamma RII. The authors have now investigated whether one of the isoforms of hFc gamma RII is also responsible for the polymorphism in binding of mIgG2b. In these studies the authors used EBV-transformed human B cells that dem onstrated either binding or no binding of mIgG2b in EA-rosetting assay s. mRNA obtained from these cells was amplified by reverse transcripta se and polymerase chain reaction (RT-PCR). Hybridization experiments w ith the RT-PCR products revealed that the hFc gamma RIIB but not the h Fc gamma RIIA isoform was present in these cells. DNA sequencing furth er demonstrated that the nucleotide sequence of both the extracellular part and the cytoplasmic moiety of hFc gamma RIIB was identical for a ll individuals tested, regardless of their ability to bind mIgG2b. The se findings indicate that the polymorphic binding of mIgG2b cannot be ascribed to one of the isoforms of hFc gamma RII. Since hFc gamma RI a nd hFc gamma RIII are not present on the cell surface of these cells, the authors conclude that an Fc receptor different from the known hFc gamma receptors must be responsible for the polymorphic binding of mIg G2b. These data further expand the complexity of hFc gamma R.