Practice question

Rituximab first chimeric mouse-human IgG1 kappa mAb targeting CD20 tetra-spanning membrane protein 33-37 kDa encoded MS4A1 11q12 four hydrophobic transmembrane domains intracellular N C termini extracellular small large loops 44 aa large loop epitope. CD20 forms homodimers tetramers lipid rafts regulating calcium flux store-operated entry Orai1 STIM1 and BCR signaling amplifying PLC gamma. Expression pre-B mature B lymphocytes but absent plasma cells HSC no shedding soluble form slow internalization excellent therapeutic target. Binding rituximab large loop crosslinks CD20 redistribution lipid rafts activating Src kinases Lyn Fyn phosphorylating ITAM leading caspase-3/9 dependent apoptosis mitochondrial cytochrome c release PARP cleavage. Fc effector potent complement-dependent cytotoxicity initiated C1q binding CH2 forming C4b2a C3 convertase lysing cells especially high CD20 density NHL plus ADCC via Fc gamma RIIIa V158F polymorphism high affinity correlating response enhanced NK activity ADCP macrophages. B-cell depletion blood 24h lasts 6-9 months while plasma cells lacking CD20 preserve preexisting IgG titers allowing regeneration CD20-negative pro-B progenitors without prolonged hypogammaglobulinemia but increasing infection risk nadir requiring monitoring.