HYALURONATE-CD44 INTERACTIONS CAN INDUCE MURINE B-CELL ACTIVATION

CD44 is a widely distributed cell surface glycoprotein whose principal ligand has been identified as hyaluronic acid (HA), a major component of the extracellular matrix (ECM). Recent studies have demonstrated t hat activation through CD44 leads to induction of effector function in T cells and macrophages. In the current study, we investigated whethe r HA or monoclonal antibodies (MoAbs) against CD44 would induce a prol iferative response in mouse lymphocytes. Spleen cells from normal and nude, but not severe combined immunodeficient mice, exhibited strong p roliferative responsiveness to stimulation with soluble HA or anti-CD4 4 MoAbs. Furthermore, purified B cells, but not T cells, were found to respond to HA. HA was unable to stimulate T cells even in the presenc e of antigen presenting cells (APC) and was unable to act as a costimu lus in the presence of mitogenic or submitogenic concentrations of ant i-CD3 MoAbs. In contrast, stimulation of B cells with HA in vitro, led to B-cell differentiation as measured by production of IgM antibodies in addition to increased expression of CD44 and decreased levels of C D45R. The fact that the B cells were responding directly to HA through its binding to CD44 and not to any contaminants or endotoxins was dem onstrated by the fact that F(ab), fragments of anti-CD44 MoAbs or solu ble CD44 fusion proteins could significantly inhibit the HA-induced pr oliferation of B cells. Also, HA-induced proliferation of B cells was not affected by the addition of polymixin B, and B cells from lipopoly saccharide (LPS)-unresponsive C3H/HeJ strain responded strongly to sti mulation with HA. Furthermore, HA, but not chondroitin-sulfate, anothe r major component of the ECM, induced B-cell activation. It was also n oted that injection of HA intraperitoneally, triggered splenic B cell proliferation in vivo. Together, the current study demonstrates that i nteraction between HA and CD44 can regulate murine B-cell effector fun ctions and that such interactions may play a critical role during norm al or autoimmune responsiveness of B cells. (C) 1997 by The American S ociety of Hematology.