FIGURE 3.

Targets for monoclonal antibodies in B cells for the MN therapy strategy. B cells originated from bone marrow stem cells as pro-B cells and mature to pre-B cells, immature B cells, mature B cells, and activated B cells, which could form plasma cells, plasmablasts, and long-lived memory plasma cells that could secrete antibodies such as immunoglobulin A, immunoglobulin E, immunoglobulin G, and immunoglobulin M. Autoreactive B-cell clones could generate anti-PLA₂R and anti-THSD7A antibodies. When B cells became mature, they generated many biomarkers that were considered targets for monoclonal antibodies. Monoclonal antibodies rituximab and ofatumumab could bind and inhibit a number of CD20-positive B cells but not mature plasma cells, plasmablasts, and memory plasma cells that could not produce CD20 antigen. Plasma cells produced CD38 and could be a target for anti-CD38 antibodies by daratumumab and isatuximab. Immature, mature, and activated B cells produced receptors for B-lymphocyte stimulator including B-cell activating factor receptor, B-cell maturation antigen, transmembrane activator, and calcium-modulating cyclophilin (TACMC) ligand interactor. Belimumab could inhibit B-cell differentiation into plasma cells by suppressing interaction between B-lymphocyte stimulator and its receptors. Bortezomib, a proteasome inhibitor, could inhibit antibody production by mediating plasma cell apoptosis, while anti-CD38 antibodies daratumumab and isatuximab could directly mediate plasma cell cytolysis.