Figure 2.

FcRn mediated IgG recycling pathway and antibody mediated antigen removal via pH dependent binding. (A) IgG circulating in the blood is taken up by endothelial cells or monocytes through either fluid phase pinocytosis or receptor mediated endocytosis. Once inside the cells, IgG binds to FcRn in the acidified endosomes. IgG that binds to FcRn migrates to the cell surface where the IgG encounters a physiological pH environment (~pH 7.4) and is released back into the blood. IgG that is not bound to FcRn (due to competition with other IgG) will be sorted to lysosomes for degradation. (B) mAb (with strong binding at pH 7.4 and no or weak binding at pH 6) binds to antigen at neutral pH in the circulation; once endocytosed into the cell and entered the acidic endosome, the antibody releases the antigen and binds to FcRn. FcRn bound antibody recycles back to the blood stream while the antigen is degraded in the lysosome