Fig. 8. Schematic representation of proposed mechanisms of CD21 shedding activation. Activation of B cells by BCR and CD40 crosslinking leads to a tyrosine phosphorylation pathway that involves PKC. A similar pathway is activated by pervanadate in B cells, as well as in non-lymphoid cells such as the epithelial cell line 293. Subsequently, a serine protease is activated that is necessary to activate the metalloprotease involved in CD21 shedding. Thiol antioxidants such as NAC directly activate the metalloprotease and open disulfide bridges within the SCRs of CD21. This leads to the formation of a stalk region that permits access of the protease to the cleavage site within SCR16. PMA, phorbol 12-myristate 13-acetate, PTP, protein tyrosine phosphatase; PTK, protein tyrosine kinase; MMP, metalloprotease; TyrP, tyrosine-phosphorylated protein; Bim, bisindolyl maleimid; NAC, N-acetyl cysteine; PKC, protein kinsae C.