MABC987 Sigma-AldrichAnti-Semaphorin 4D/CD100 Antibody, clone BMA-12

CD100 participates in adaptive immune responses and is important in neural cell migration. To determine the role of endogenous CD100 in severe glomerular inflammation, we induced experimental crescentic glomerulonephritis by planting a foreign antigen in glomeruli of sensitized normal and CD100-deficient (CD100(-/-)) mice. Fewer CD100(-/-) glomeruli exhibited crescent formation or severe histological changes. Antigen-specific immune responses were reduced in CD100(-/-) mice. There was less interferon (IFN)-gamma and interleukin (IL)-4 production by splenocytes and fewer activated T and B cells were present in lymph nodes of immunized CD100(-/-) mice. Serum antigen-specific immunoglobulin (IgG) levels were also decreased. Glomerular macrophage and CD4(+) cell infiltration, and IgG and C3 deposition were attenuated. Normal kidneys expressed mRNA for CD100 and plexin-B1 (the tissue receptor of CD100). Direct immunofluorescence showed that renal-CD100 protein was predominantly in tubules, while plexin-B1 was present in both glomeruli and tubules. To determine whether glomerular plexin-B1 mediates leucocyte recruitment via leucocyte CD100, recruitment was studied after passive transfer of heterologous antibody (attracting neutrophils) or isologous antibody (attracting macrophages). Glomerular macrophages were reduced in CD100(-/-) mice, but neutrophil recruitment was equivalent, consistent with CD100 expression on macrophages, but not neutrophils. CD100 promotes severe nephritogenic immune responses and leucocyte CD100-glomerular plexin-B1 interactions enhance macrophage recruitment to glomeruli.

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)

We have identified the lymphocyte semaphorin CD100/Sema4D as a CD40-inducible molecule by subtractive cDNA cloning. CD100 stimulation significantly enhanced the effects of CD40 on B cell responses. Administration of soluble CD100 markedly accelerated in vivo antigen-specific antibody responses. CD100 receptors with different binding affinities were detected on renal tubular cells (K(d) = approximately 1 x 10(-9)M) and lymphocytes (K(d) = approximately 3 x 10(-7)M). Expression cloning revealed that the CD100 receptor on lymphocytes is CD72, a negative regulator of B cell responsiveness. CD72 thus represents a novel class of semaphorin receptors. CD100 stimulation induced tyrosine dephosphorylation of CD72 and dissociation of SHP-1 from CD72. Our findings indicate that CD100 plays a critical role in immune responses by the novel mechanism of turning off negative signaling by CD72.