Autocrine proliferating B cells are susceptible to terminal differentiation and apoptosis

Lymphocytes that proliferate autonomously are thought to be arrested at certain steps in differentiation. Here we demonstrate that autocrine proliferating B cells can be induced to terminal differentiation in the presence of ionomycin plus phorbol dibutyrate. The mature CD23high/CD38low B cell phenotype converts to the CD23low/CD38high plasma cell phenotype associated with increased immunoglobulin secretion and PC1 expression and a loss in surface immunoglobulin. Simultaneously, the cells arrest in proliferation and enter apoptosis at day 10. The cytokines IL-1alpha, IL-6, TNFalpha and TNFbeta that are required to sustain continuous growth are secreted in substantially increased amounts mediating entry into apoptosis of the proliferating cells. Decrease in IL-10 secretion sustains this process. Our results draw the concept that once plasmacytoid differentiation is initiated, the growth sustaining network of autocrine cytokines is disturbed in a particular fashion depriving appropriate signals to suppress the differentiation associated apoptotic program.