Monoclonal antibodies are able to block ligand-receptor bindings and induce antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) in vivo. In ADCC, the Fc region of an antibody binds to Fc receptors (FcγRs) on the surface of immune effector cells such as natural killers and macrophages, leading to phagocytosis or lysis of the targeted cells. In CDC, the antibodies kill the targeted cells by triggering the complement cascade at the cell surface. The use of xenogeneic antibodies, i.e., the monoclonal antibodies derived from human or rat, may cause severe CDC effects in various mouse models.
Mouse cells express different types of Fc receptors, e.g. FcγRI, FcγRII, FcγRIII, and FcγRV, which show different binding affinities to immunoglobulin (Ig) G subclasses (vide infra). Therefore, one isotype of IgG molecule may only target a group of cells that express the cognate Fc receptor in the cell membrane. IgG subclasses exert different levels of effector functions of ADCC in the increasing order of IgG1 < IgG3 < IgG2a ≈ IgG2b. The induction of systemic ADCC effects may require the infusion of a mixture of IgG isotypes.
| Fc receptor type | FcγRI | FcγRII | FcγRIII | FcγRV | |
| Cellular expression | T cell | + | – | – | – |
| B cell | – | + | – | – | |
| NK cell | – | – | + | – | |
| Neutrophil | – | + | + | + | |
| Dendritic cell | + | + | + | + | |
| Binding affinity | IgG1 | – | ++ | + | – |
| IgG2a | +++ | + | + | ++++ | |
| IgG2b | + | ++ | + | ++++ | |
| IgG3 | + | – | – | – |
BiCellVivo anti-mouse PD-L1 (CD274 or B7-H1) antibody is a recombinant chimeric antibody consisting in the Fv domain from the rat anti-mouse PD-L1 antibody (clone 10F9G2) and the Fc domain from each of the four subclasses of mouse IgG protein, IgG1, IgG2a, IgG2b, and IgG3. BiCellVivo anti-mouse PD-L1 (CD274 or B7-H1) antibody is recommended to use with the class-matching isotype control antibody (Cat No: BCVI00).
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