Cell-cell interactions and cytoskeleton organization are involved in MCL cell death evoked by immobilized rituximab and milatuzumab. Jeko (A) and Mino (B) cells were treated with dimethylsulfoxide (DMSO) or the actin polymerization inhibitor, latrunculin B (10μM), for 45 minutes before the addition of rituximab and milatuzumab, in the presence of a cross-linking antibody. Cell aggregation was assessed 4 hours later by light microscopy. Pretreatment with latrunculin B significantly reduced cell aggregation. Jeko (C) and Mino (D) cells were treated with DMSO or an actin polymerization inhibitor (latrunculin B), for 45 minutes before the addition of rituximab and milatuzumab in the presence of a rhodamine-conjugated cross-linking antibody. The formation of aggregates and caps are shown on Jeko in panel C (left) and Mino in panel D (left) cell surface was evaluated 4 hours later by confocal microscopy. Representative histograms summarizing the percentage of capped cells in the presence or absence of latrunculin B are shown in panel C (Jeko right) and panel D (Mino right). At least 100 cell/conditions were counted for each of the 3 independent experiments. Pretreatment with latrunculin B significantly (P < .01) reduced the capping and colocalization of CD74 and CD20 antigens. Cell death evaluation of Jeko (E) and Mino (F) cells treated with DMSO or latrunculin B, for 45 minutes before the addition of rituximab and milatuzumab in the presence of a cross-linking antibody. Cell death was determined 4 hours later by AnnexinV–PI and flow cytometry. Pretreatment with lactrunculin B resulted in statistically significant reduced cell death induced by the combination treatment (P < .01).