Rituximab capping triggers intracellular reorganization of B cells

The antibody rituximab, which binds to the protein CD20 on the surface of B-cells, has been used to treat B-cell malignancies for several years. However, the molecular mechanisms underlying this treatment are not yet fully understood. One well-established rituximab-induced mechanism, natural killer (NK) cell mediated antibody-dependent cellular cytotoxicity (ADCC), has recently been described to involve the polarisation of bound rituximab and CD20 to one side of the B-cell. B-cells polarised this way were cleared more efficiently by NK-cells, which led us to further investigate the cellular events involved in the polarisation process. Using optical microscopy on rituximab treated cells, we have found that the rituximab/CD20-rich, polarised side accumulated mitochondria and actin, whereas the nucleus was re-organised to the opposite side of the cell. Depleting actin via different methods correlated with a decrease in rituximab, mitochondria and nucleus polarisation, suggesting polarisation to be an actin-dependent, active process that triggers intracellular rearrangement. The influence of these intracellular rearrangements on the efficiency of NK-cell mediated clearance of B-cell malignancies remains open for future investigation.