PROTEOLYSIS INCREASES THE FC-MEDIATED BINDING OF MURINE IGG2B TO HUMAN EBV-TRANSFORMED B-CELLS, BUT DECREASES THE EXPRESSION OF FC-GAMMA-RII AND FC-EPSILON-RII

We have previously described a polymorphic human Fc receptor for murin e IgG2b (mIgG2b). This receptor was defined by the binding of (complex ed) mIgG2b to monocytes and Epstein-Barr virus (EBV)-transformed B cel ls. Three per cent of normal individuals were high responders with res pect to mIgG2b (mIgG2b-HR), whereas the other individuals were low res ponders for mIgG2b (mIgG2b-LR). In the present study we investigated t he effect of proteolytic enzymes on the Fc-mediated binding of mIgG2b to EBV-B cells. Pronase, human leucocyte elastase and cathepsin G caus ed an increased binding (in an EA-rosetting assay) of mIgG2b to EBV-B cells from mIgG2b-HR, but not from mIgG2b-LR. Simultaneous immunofluor escence studies demonstrated that these proteolytic enzymes strongly r educed the expression of FcgammaRII and FcepsilonRII on these cells, w hereas HLA class I or HLA class II molecules were not affected. These findings strongly suggest that binding of mIgG2b is not mediated by Fc gammaRII or FcepsilonRII. We also studied the effect of proteolysis on mIgG2b-HR EBV-B cells from an HLA class II-negative individual. In th is case EA-mIgG2b rosetting was decreased after proteolysis, suggestin g that HLA class II molecules may have a role in protecting the bindin g site for mIgG2b against proteolytic destruction.