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. This 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-gamma and to some extent by IL-4. Investigation of the potential molecular mechanism involved revealed that PMA-induced HA adhesion correlated with enhanced expression of CD44-H- and V6-containing isoforms, as determined by flow cytometry, and the differential induction of V4- and V5-containing isoforms, as determined by reverse transcriptase-based polymerase chain reaction analysis. The inhibition of PMA-induced adhesion by IFN-gamma and IL-4 correlated with the downregulation of CD44 H expression and altered usage of exons V4 and V5. However, changes in the electrophoretic mobility of CD44 proteins, as a measure of posttranslational modifications, were not detected in 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 influence B cell migration through their ability to downregulate CD44-HA interactions.