Induction of Proliferation and Differentiation of Leukaemic B Cells from Patients with Chronic Lymphocytic Leukaemia by Anti‐μ and Conditioned Medium

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Abstract
We investigated the growth and differentiation of leukaemic B cells from patients with B-cell chronic lymphocytic leukaemia (CLL) in response to proliferation and differentiation factors present in conditioned medium and to anti-immunoglobulin antibodies. High purified E-rosette negative (E-) B cells from 5 out of 15 patients with CLL exhibited moderate proliferative responses to 10 or 50 .mu.g/ml of F(ab)''2 fragment of rabbit anti-human .mu.-chain specific antibody. Conditioned medium (CM), derived by stimulating human peripheral blood mononuclear leucocytes with PHA, induced significant proliferative responses of purified E- cells in 13 out of 14 patients examined. The extent of these proliferative responses varied substantially, and was in the range of 2.6- to 91-fold. Stimulation of purified E- cells from patients with CLL wtih both anti-.mu. and CM resulted in significant proliferation in all 15 patients examined. These responses were significantly higher than those induced by CM alone (P < 0.02). Synergism between CM and anti-.mu. in inducing proliferative responses was observed in 11 out of 15 patients. Largely leukaemic B cell populations expressing on the cell surface more than one immunoglobulin heavy-chain isotype, exhibited significantly higher (P < 0.009) proliferative response to CM and anti-.mu. than those expressing IgM only. Highly purified E- peripheral blood or tonsil lymphocytes from all normal donors examined responded by proliferation to anti-.mu. alone or to CM alone. Synergism in inducing proliferative responses was also observed when the cells were stimulated with both CM and anti-.mu.. In addition to inducing proliferative responses, culture with CM of purified E-rosette negative, largely leukaemic, B cells from patients with CLL for 6 days at 37.degree. C resulted in differentiation into immunoglobulin synthesizing and screening cells. Synthesis and secretion of IgM were observed in 7 out of 10 patients examined. A switch to IgG production was observed in three patients. Morphological examination of E- cells from patients with CLL after treatment with CM demonstrated that these cells were differentiated into plasma-like cells. These results suggest that in leukaemic B cells from patients with CLL can be induced to proliferate and differentiate in response to growth and differentiation factors derived by mononuclear leucocytes, in a manner similar to that of normal B cells.