Interferon-gamma inhibits CD44-hyaluronan interactions in normal human B lymphocytes

The interaction of CD44 with its ligand hyaluronan (HA) plays a vital role in lymphopoiesis, lymphocyte homing, T cell activation, and metastasis. Thi s study addresses the effect of cytokines involved in B cell growth on CD44 -HA interactions in normal human B cells. Activation of B lymphocytes with LPS, pokeweed mitogen, or anti-IgM antibodies with or without IL-2 or IL-4 failed to induce HA adhesion. Stimulation of B cells with the phorbol ester PMA, however, induced strong HA recognition, which was inhibited by IFN-ga mma and to some extent by IL-4. Investigation of the potential molecular me chanism involved revealed that PMA-induced HA adhesion correlated with enha nced expression of CD44-H- and V6-containing isoforms, as determined by flo w cytometry, and the differential induction of V4- and V5-containing isofor ms, as determined by reverse transcriptase-based polymerase chain reaction analysis. The inhibition of PMA-induced adhesion by IFN-gamma and IL-4 corr elated with the downregulation of CD44 H expression and altered usage of ex ons V4 and V5, However, changes in the electrophoretic mobility of CD44 pro teins, as a measure of posttranslational modifications, were not detected i n response to PMA and IFN-gamma or PMA and IL-4, These results suggest that the inhibition of PMA-induced HA adhesion by IFN-gamma and IL-4 may influe nce B cell migration through their ability to downregulate CD44-HA interact ions. (C) 1999 Academic Press.