Senescence of a Human Lymphoblastoid Clone Producing Anti-Rhesus(D)

The exploitation of Epstein-Barr virus transformation to generate human lymphoblastoid clones (LCL) producing antibody of predefined specificity has proved highly inefficient. Observations reported here on a cloned LCL producing anti-Rhesus(D) may provide an explanation for the low success rate. Over a few months this clone manifested a progressive loss of capacity to maintain growth in culture. Evidence consistent with terminal differentiation to a cell with the properties of a nonproliferating plasma cell was obtained. These late cells differed from those in the earlier actively cycling phase in that they were no longer able to respond to autostimulatory growth factors although they continued to produce them. This irreversible senescence leading to the death of the clone may be a common feature of virally transformed B cells and this would explain many of the difficulties encountered on this route to the production of human monoclonal antibodies.