PHENOTYPIC, MORPHOLOGIC CHANGES AND IG SECRETION INDUCED ON B-NHL CELLS IN-VITRO BY INTERFERON-ALPHA AND ALL-TRANS-RETINOIC ACID - POSSIBLEPROGRESSION TOWARD A MORE DIFFERENTIATED STATE

Twenty-five B-cell-nonHodgkin's lymphomas (B-NHL): 6 lymphocytic, 2 ce ntrocytic, 13 follicular, centrocytic/centroblastic, 2 lymphoplasmocyt oid and 2 centroblastic were tested for their ability to acquire featu res of mature plasma cells under the effect of interferon alpha (final concentration, 600 UI/ml), all-trans-retinoic-acid (ATRA) (final conc entration, 10(-6) mol/l) and the association of both. B-NHL cells were negatively purified (>99%) by an immunomagnetic method, cultured for 7 d with or without interferon and ATRA, then stained with anti-CD19, CD20, surface Ig, DR, CD38 and with anti-CD138 (syndecan-1) antibody-r ecognizing plasma cells. Ig production was estimated in culture supern atants by an ELISA method and changes in cell morphology were investig ated on May-Grunwald-Giemsa-stained cytospin preparations. In all case s interferon and ATRA, alone or in association, were able to induce ch anges in the immunophenotypic profile, associated or not with morpholo gic changes and induction of Ig secretion. All changes were greatly va riable from one to the other B-NHL sample and no relationship could be found between a particular pattern of change and the histological sub type. Interferon alpha was more potent than ATRA in inducing changes. In favour of a differentiation process, we observed a concomitant decr ease of DR expression and increase of CD38 expression in 8 cases with interferon alpha, and in 4 cases with ATRA. Although interferon- or AT RA-treated cells did not display cytologic, functional features and ch anges of the immunophenotypic profile fully compatible with those of t erminally differentiated cells, these results suggest a possible trans ition toward more differentiated elements, especially with interferon alpha.