Induction of differentiation in human leukemic B cells by interleukin 2 alone: differential effect on the expression of mu and J chain genes

Abstract

The effects of interleukin 2 (IL2) on the proliferation and differentiation of B cells were analyzed separately using cells from two patients suffering from B-type chronic lymphocytic leukemia. The monoclonal B cells from these patients exhibited an opposite pattern of responsiveness upon in vitro culture with IL2 in the absence of other stimuli. In the first patient, IL2 alone was able to induce DNA synthesis and no Ig production. In the second patient, although no DNA synthesis was detected, B lymphocytes synthesized IgM upon stimulation with IL2 alone. Analysis of mRNA levels was performed on the cells of this latter patient after culture without or with IL2. In the presence of IL2 we observed a strong enhancement of C mu gene expression associated with an increase of the ratio between the secreted form and the membrane-bound form of mu mRNA. In contrast IL2 induced only a marginal enhancement of J chain mRNA. Thus, terminal B cell differentiation of selected monoclonal B cells can be obtained in the absence of DNA synthesis and IL2 alone can mediate this process. Moreover, IL2 can act at selective steps of the molecular events associated with IgM production. These results document the multiple effects of a given IL on the events leading to antibody production and strongly suggest that they can be conditioned by the maturation stage of a given responding cell.