Functional soluble CD100/Sema4D released from activated lymphocytes: possible role in normal and pathologic immune responses

CD100/Sema4D is a 150-kd transmembrane protein that belongs to the semaphor in family. The interaction of CD100 with CD72 is critical for the immune sy stem. in CD100-deficient mice, the production of specific antibodies agains t T-cell-dependent antigens is severely impaired, but not against T-cell-in dependent antigens. Here, a functional soluble CD100 protein (sCD100) relea sed from activated lymphocytes is reported. sCD100 was detected in culture supernatants of activated lymphocytes, Either affinity-purified from supern atants of activated T-cells, or produced as a recombinant sCD100 protein co nsisting of the extracellular region of the moose CD100 fused to the human IgG1 Fc(CD100-Fc), sCD100 significantly enhanced CD40-induced B-cell respon ses. Furthermore, sCD100 was detected either in sera of mice immunized with T-cell-dependent antigens, or in sera of MRL/lpr mice, but not in sera of mice immunized with T-cell-independent anti-gens, A significant correlation was observed between the level of sCD100 and the titer of autoantibodies i n the serum of MRL/lpr mice. This study's findings suggest a potential role for sCD100 in immune responses, including production of antibody, and auto immune diseases. (Blood, 2001;91: 3498-3504) (C) 2001 by The American Socie ty of Hematology.