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 semaphorin family. The interaction of CD100 with CD72 is critical for the immune system. In CD100-deficient mice, the production of specific antibodies against T-cell-dependent antigens is severely impaired, but not against T-cell-independent antigens. Here, a functional soluble CD100 protein (sCD100) released from activated lymphocytes is reported. sCD100 was detected in culture supernatants of activated lymphocytes. Either affinity-purified from supernatants of activated T-cells, or produced as a recombinant sCD100 protein consisting of the extracellular region of the mouse CD100 fused to the human IgG1 Fc (CD100-Fc), sCD100 significantly enhanced CD40-induced B-cell responses. 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 antigens. A significant correlation was observed between the level of sCD100 and the titer of autoantibodies in the serum of MRL/lpr mice. This study's findings suggest a potential role for sCD100 in immune responses, including production of antibody, and autoimmune diseases. (Blood. 2001;97:3498-3504)
Wang
X
X
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Kumanogoh
A
A
Watanabe
C
C
Shi
W
W
Yoshida
K
K
Kikutani
H
H
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D015703:Antigens, CD; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D039961:Semaphorins; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*
D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D001323:Autoantibodies; C093224:CD100 antigen; D008562:Membrane Glycoproteins; D039961:Semaphorins