Phorbol Ester Induction of Ia and a Shared B-Cell/T-Cell Phenotype in Normal but Not Autoimmune (lpr) Mice

Tumour-promoting phorbol diesters are mitogenic for lymphocytes and induce differentiation of B and T cell lines as well as promyelocytic leukaemia cells. This paper demonstrates that 12-O-tetradecanoyl-13-acetate (PMA), when cocultured with normal murine bone marrow cells (BMC), significantly augments an antigenic cell-surface determinant called 14D10. This antigen is present constitutively in the majority of bone-marrow lymphocytes of autoimmune lpr mice. PMA has little enhancing effect when cocultured with lpr BMC. In addition, Ia antigenic determinants are increased by PMA in normal but not lpr BMC. Retinoic acid (RA) and PMA act synergistically both to increase 14D10 and to enhance the stimulatory ability of target lymphocytes as measured by proliferation in an autologous mixed lymphocyte reaction (AMLR). We suggest that lpr mice have persistent expression of gene products like 14D10 that are usually repressed in normal adult mice. These gene products can be activated in normal mouse bone marrow by PMA which acts through a Ca2+-dependent phospholipid-dependent C protein kinase. The in vivo enhanced expression of 14D10 in lpr mice suggests activation by some mechanism or factors yet to be described.