At nanomolar concentrations,
phorbol 12-myristate 13-acetate induced differentiation in a human Epstein-Barr virus-negative B-cell line, JD 38, derived from an
undifferentiated lymphoma and containing an 8;14 translocation. The changes induced by
phorbol 12-myristate 13-acetate were consistent with differentiation towards plasma cells and included (i) a marked increase (30-fold) in
IgM secretion; (ii) a decrease in the nuclear/cytoplasmic ratio associated with the development of a single prominent nucleolus instead of multiple nucleoli; (iii) the development of parallel arrays of rough endoplasmic reticulum, eccentric nuclei, and marginated
heterochromatin; (iv) a reduction in the expression of surface markers, including common
acute lymphoblastic leukemia antigen,
IgM, and C3 receptors. Essentially all cells showed plasmacytoid differentiation, although the degree varied. Rare cells (less than 1%) appeared to be terminally differentiated into plasma cells. The increase in secreted
IgM was preceded by a small increase in mu-chain
RNA, with an increase in the ratio of secreted to membrane form. A small increase in c-myc
RNA was also detected with differentiation. This might reflect coordinate regulation of the transcription of
immunoglobulin and the translocated c-myc gene. Thus, the maturational arrest of this
lymphoma cell line can be overcome with
phorbol 12-myristate 13-acetate, indicating that translocation of the c-myc gene does not permanently block the capacity for differentiation. Further, this gene continues to be expressed to at least the same level during cell maturation. Similar ultrastructural changes were induced by
phorbol 12-myristate 13-acetate in four of seven additional lines studied.