Biologic effect of cross-linking multivalent anti-CD20/CD74 bispecific antibodies in B-cell lymphomas. Aggregation of lymphoma cells by bispecific antibodies causes reorganization of actin and migration of antigen (red) into lipid rafts that in turn induces the release of lysosomal cathepsin B and reactive oxygen species (ROS) and influx of calcium ions into mitochondria. Swollen lysosomes and mitochrondria are accompanied by the deactivation of the PI3K/Akt signaling pathway and the rapid and sustained activation of ERK, JNK, and MAPKs associated with cell death. Nonaggregated cells remain viable in the absence of antibody binding.