We have monitored Fc gamma RII expression during the activation of human B lymphocytes by simultaneous analysis of monoclonal antibody (mAb) binding and EA rosetting. The expression of Fc gamma RII showed a biphasic time course. Initially, a transient increase of Fc gamma RII with no ligand-binding capacity was observed with mAb staining as early as 10 min after stimulation by the F(ab')2 fragment of anti-human IgM or phorbol 12-myristate 13-acetate and then after 3 to 24 h a decrease in the number of Fc gamma RII+ cells was seen. Trypsin-like serine protease activity also appeared in the lysate of activated B cells at this time. On the 2nd day of activation a significant enhancement of Fc gamma RII expression was observed, mainly on enlarged blast cells as monitored by both mAb and by ligand binding (EA rosette). At the same time, soluble fragments of Fc gamma RII with the ability to bind human Fc were detected in the supernatant of activated B cells, probably as a result of proteolytic cleavage. These findings suggest that activated B cells are identical with the population of mononuclear cells which shed Fc gamma R when incubated at 37 degrees C. The ability of activated but not resting B cells to release Fc gamma RII correlates with the expression of early activation markers and with the appearance of a trypsin-like serine protease activity of the same cells; thus, the release of Fc gamma RII occurs in the early G1 phase of cell cycle as a result of proteolysis. Later the release of Fc gamma RII is accompanied by the enhancement of Fc gamma RII expression before the cells reach the S phase. The fragments of cleaved Fc gamma RII had an apparent molecular mass of 33 and 14-18 kDa under nonreducing conditions, and upon reduction fragments of smaller size were observed.