DIFFERENTIAL SIGNAL REQUIREMENT FOR UP-REGULATION OF HLA-CLASS-II MOLECULES IN HUMAN LYMPHOMA B-CELLS

HLA-class II molecules can be induced in low-grade non-Hodgkin B lymph oma cells by either membrane IgM cross-linking orphorbolester stimulat ion. The ability of phorbolesters to substitute for anti-IgM antibodie s in the activation of normal and malignant human B cells has been tak en as evidence for the involvement of protein kinase C (PKC) in signal s transduced through membrane IgM receptors (mIgR). Here we report on freshly isolated lymphoma B cells from different patients; the cells s how a distinct regulation of HLA-class II expression. In certain lymph oma cases phorbol-myristate-acetate (PMA) not only fails to upregulate HLA-class II molecules but also inhibits anti-IgM or interleukin-4 in duced class II expression. This negative signal induced by PMA seems t o operate specifically in HLA-class II regulation because PMA can indu ce other anti-IgM mediated events like blast transformation and induct ion of IL-4 responsiveness at the same time. Therefore these cells sup port the concept of functional heterogeneity in low-grade non-Hodgkin lymphoma and may represent a differentiation stage where anti-IgM anti bodies and phorbolesters influence the regulation of HLA-class II expr ession in a contrary direction.