Phorbol ester-induced differentiation of chronic B lymphocytic leukaemia cells--regulatory impact of autologous and allogeneic accessory cells
Danersund, A.; Tötterman, T.H.; Nilsson, K.; Egle-Jansson, I.; Kabelitz, D.; Sjöberg, O.
Clinical and Experimental Immunology 59(3): 644-652
1985
ISSN/ISBN: 0009-9104 PMID: 3872753 Document Number: 249524
Phorbol ester (TPA) induction of chronic lymphocytic leukemia (CLL) cells can be used as a model system for the study of human B cell differentiation. The role of accessory cells and the correlation to target cell surface Ig phenotype in TPA-induced morphological and functional differentiation of 12 CLL populations were analyzed. A > 3-fold increase in secreted IgM was seen in 10 of 12 cases, with the strongest responses in patients having monoclonal serum IgM. CLL populations negative for or having only weak surface .mu. chain expression were less inducible. The impact of autologous and allogeneic accessory cells on TPA induction was studied in cell enrichment/depletion experiments using physical and cytotoxic antibody techniques. CLL cells physically depleted of autologous E+ [sheep erythrocyte rosette-forming] and monocytic (light density fraction) cells still responded to TPA. This response could be enhanced by allogeneic E- light fraction cells. Further depletion of autologous accessory cells by treatment of the E- high density fraction CLL cells with a panel of monoclonal antibodies plus complement demonstrated the permissive role of 1 or 2 populations of autologous cells expressing low avidity E receptors and the T3, T4 and T8 antigens. Augmenting T cells of similar phenotype were found among allogeneic cells from normal individuals. Thus, TPA-induced IgM secretion in biopsy B-CLL cells is regulated by minute numbers of autologous helper T cells. The Ig secretory response of CLL populations seems to be correlated with the surface Ig phenotype of the leukemic cells.