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| Hyaluronate-CD44 interactions can induce murine B-cell activation |
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| Author(s): Rafi A, Nagarkatti M, Nagarkatti PS |
| Source: BLOOD Volume: 89 Issue: 8 Pages: 2901-2908 Published: APR 15 1997 |
| Times Cited: 59 References: 31 |
| Abstract: 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 that activation through CD44 leads to induction of effector function in T cells and macrophages. In the current study, we investigated whether HA or monoclonal antibodies (MoAbs) against CD44 would induce a proliferative response in mouse lymphocytes. Spleen cells from normal and nude, but not severe combined immunodeficient mice, exhibited strong proliferative responsiveness to stimulation with soluble HA or anti-CD44 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 presence of antigen presenting cells (APC) and was unable to act as a costimulus in the presence of mitogenic or submitogenic concentrations of anti-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 CD45R. The fact that the B cells were responding directly to HA through its binding to CD44 and not to any contaminants or endotoxins was demonstrated by the fact that F(ab), fragments of anti-CD44 MoAbs or soluble CD44 fusion proteins could significantly inhibit the HA-induced proliferation of B cells. Also, HA-induced proliferation of B cells was not affected by the addition of polymixin B, and B cells from lipopolysaccharide (LPS)-unresponsive C3H/HeJ strain responded strongly to stimulation with HA. Furthermore, HA, but not chondroitin-sulfate, another major component of the ECM, induced B-cell activation. It was also noted that injection of HA intraperitoneally, triggered splenic B cell proliferation in vivo. Together, the current study demonstrates that interaction between HA and CD44 can regulate murine B-cell effector functions and that such interactions may play a critical role during normal or autoimmune responsiveness of B cells. (C) 1997 by The American Society of Hematology. |
| Document Type: Article |
| Language: English |
Addresses:
1. VIRGINIA POLYTECH INST & STATE UNIV, DEPT BIOL, DIV MICROBIOL & IMMUNOL, BLACKSBURG, VA 24061 USA
2. VIRGINIA POLYTECH INST & STATE UNIV, VIRGINIA MARYLAND REG COLL VET MED, BLACKSBURG, VA 24061 USA |
| Publisher: W B SAUNDERS CO, INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 |
| Subject Category: Hematology |
| IDS Number: WV146 |
| ISSN: 0006-4971 |
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