Apoptosis induced by crosslinking of CD4 on activated human B cells

Using immunofluorescence, RT-PCR, and Western blotting, we have demonstrate d the ability of human B cells to express CD4. In each of the 10 lymphoblas toid cell lines (LCL) tested there was variable, but definite, proportion o f CD4-positive B cells. Expression of CD4 was related to the cell cycle; CD 4 was expressed in the G1 phase and continued at later phases of the cell c ycle, CD4 was in part internalized and degraded by the LCL B cells. Surface CD4 was associated to Let and its crosslinking resulted in tyrosine phosph orylation. Additional experiments conducted on freshly prepared tonsillar B cells demonstrated that CD4 was expressed by large activated B cells, but not by small resting B cells. However, not all the activated tonsillar B ce lls had surface CD4 since germinal center cells were GD4-negative. Crosslin king of CD4 on LCL or on tonsillar activated B cells resulted in apoptosis in vitro, a finding that indicates the capacity of CD4 to deliver functiona l signals to B cells and to play a regulatory function in their physiology. Exposure of CD4 expressing B cells to gp120 under conditions that resulted in CD4 crosslinking also caused apoptosis suggesting some implications for the pathophysiology of AIDS. (C) 1999 Academic Press.