A polymorphic Fc receptor for mouse IgG2b on human B cells and monocytes.

With respect to murine (m)IgG1 anti-CD3 monoclonal antibody (mAb), a polymorphic mitogenic response of peripheral blood mononuclear cells (PBMC) has been described which is caused by polymorphism of monocyte Fc gamma RII, and which defines high responders to mIgG1 (mIgG1-HR, approximately 70% of normal individuals) and low responders (mIgG1-LR). PBMC also exhibit a polymorphic mitogenic response to mIgG2b anti-CD3 mAb. In the present study 18 out of 550 individuals (3%) were mIgG2b-HR. Purified monocytes from mIgG2b-HR were able to support the mitogenic response to mIgG2b anti-CD3 mAb of purified T cells from mIgG2b-LR. Surprisingly, a significant mitogenic response to mIgG2b anti-CD3 mAb remained after vigorous depletion of monocytes from mIgG2b-HR PBMC. Apparently B cells are responsible for this accessory function since Epstein-Barr virus (EBV)-transformed B cells from mIgG2b-HR (but not from mIgG2b-LR) were able to support T-cell proliferation induced by mIgG2b anti-CD3 mAb. Only EBV B cells from mIgG2b-HR were able to form rosettes with human red blood cells (RBC) that had been sensitized with mIgG2b anti-glycophorin A mAb (EA-mIgG2b). These EBV B cells did not express Fc gamma RI or Fc gamma RIII, and could bind some but not all anti-Fc gamma RII mAb. The mitogenic response to mIgG2b anti-CD3 was not inhibited by any of the anti-Fc gamma RII mAb. From these studies we conclude that a polymorphic Fc receptor is expressed on human B cells and monocytes, which cross-reacts with mIgG2b. This receptor is different from Fc gamma RI and Fc gamma RIII, and apparently also from Fc gamma RII.