Differential signal requirement for upregulation of HLA-class II molecules in human lymphoma B cells.

HLA-class II molecules can be induced in low-grade non-Hodgkin B lymphoma cells by either membrane IgM cross-linking or phorbolester stimulation. The ability of phorbolesters to substitute for anti-IgM antibodies in the activation of normal and malignant human B cells has been taken as evidence for the involvement of protein kinase C (PKC) in signals transduced through membrane IgM receptors (mIgR). Here we report on freshly isolated lymphoma B cells from different patients; the cells show a distinct regulation of HLA-class II expression. In certain lymphoma cases phorbol-myristate-acetate (PMA) not only fails to up-regulate HLA-class II molecules but also inhibits anti-IgM or interleukin-4 induced class II expression. This negative signal induced by PMA seems to operate specifically in HLA-class II regulation because PMA can induce other anti-IgM mediated events like blast transformation and induction of IL-4 responsiveness at the same time. Therefore these cells support the concept of functional heterogeneity in low-grade non-Hodgkin lymphoma and may represent a differentiation stage where anti-IgM antibodies and phorbolesters influence the regulation of HLA-class II expression in a contrary direction.