Editors' ChoiceImmunology

Semaphorins: The CD Side of Immune Signaling

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Science's STKE  05 Dec 2000:
Vol. 2000, Issue 61, pp. tw5
DOI: 10.1126/stke.2000.61.tw5

Semaphorins are transmembrane proteins that bind neuropilins and plexins and function to regulate axon guidance. Among the known semaphorins, CD100 (also called Sema4D) is uniquely expressed in immune cells, but its function is not clear. In nonlymphoid tissues, plexin-B1 is the receptor for CD100. Kumanogoh et al. demonstrated that plexin-B1 was not expressed in B cells and T cells, and used expression cloning to identify CD72 as the immune cell receptor for CD100. Phosphorylated CD72 can bind the protein phosphatase SHP-1 and negatively regulate B cell-receptor signaling; however, Kumanogoh et al. demonstrated that CD100 caused the dissociation of SHP-1 and dephosphorylation of CD72, leading to enhanced B cell-receptor signaling. In an accompanying article Shi et al. created CD100-deficient mice and found changes in the proportions of B cell subtypes. In vitro, CD100-/- B cell proliferation was impaired, but it was rescued by treatment of cells with an antibody to CD72. Additionally, in CD100-null B cells, immunoglobulin production was deficient in vitro and in vivo, and T cell activation and cytokine production were abrogated. In CD100-deficient B cells, CD72 was constitutively phosphorylated and associated with SHP-1, which, the authors suggest, may explain why lymphocyte activation and subsequent immune responses are weak in CD100-null mice.

Kumanogoh, A., Watanabe, C., Lee, I., Wang, X., Shi, W., Araki, H., Hirata, H., Iwahori, K., Uchida, J., Yasui, T., Matsumoto, M., Yoshida, K., Yakura, H., Pan, C., Parnes, J.R., and Kikutani, H. (2000) Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: A novel mechanism for regulating B cell signaling. Immunity 13: 621-631. [Online Journal]

Shi, W., Kumanogoh, A., Watanabe, C., Uchida, J., Wang, X., Yasui, Yukawa, K., Ikawa, M., Okabe, M., Parnes, J.R., Yoshida, K., and Kikutani, H. (2000) The class IV semaphorin CD100 plays nonredundant roles in the immune system: Defective B and T cell activation in CD100-deficient mice. Immunity 13: 633-642. [Online Journal]

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