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J Biol Chem, Vol. 275, Issue 1, 548-556, January 7, 2000

The Pseudo-immunoreceptor Tyrosine-based Activation Motif of CD5 Mediates Its Inhibitory Action on B-cell Receptor Signaling^*

Hélène Gary-Gouy, Pierre Bruhns^§¶, Christian Schmitt, Ali Dalloul, Marc Daëron^§, and Georges Bismuth

From the  Laboratoire d'Immunologie Cellulaire, CNRS UMR 7627, Centre Hospitalier Pitié-Salpêtrière, CERVI, 83 Boulevard de l'Hôpital, 75013 Paris, France and the ^§ Laboratoire d'Immunologie Cellulaire et Clinique, INSERM U255, Institut Curie, 26 rue d'Ulm, 75005 Paris, France

Genetic studies revealed that CD5 could be a negative regulator of the B-cell antigen receptor (BCR). We explore here the effect of human CD5 on BCR-triggered responses. B cells were obtained expressing a chimera composed of extracellular and transmembrane domains of Fc type IIB receptor fused to CD5 cytoplasmic domain (CD5cyt). Coligation of the chimera with the BCR induces CD5cyt tyrosine phosphorylation. A rapid inhibition of BCR-induced calcium response is observed, as well as a partial but delayed inhibition of phospholipase C-1 phosphorylation. Activation of extracellular regulated kinase-2 is also severely impaired. Moreover, at the functional level, interleukin-2 production is abolished. Src homology 2 domain-bearing tyrosine phosphatase SHP-1 and Src homology 2 domain-bearing inositol 5'-phosphatase SHIP usually participate in negative regulation of the BCR. We show that they do not associate with the phosphorylated CD5 chimera. We finally demonstrate that the pseudo-immunoreceptor tyrosine based activation motif present in CD5cyt is involved because its deletion eliminates the inhibitory effect of the chimera, both at biochemical and functional levels. These results demonstrate the inhibitory role of CD5 pseudo-immunoreceptor tyrosine based activation motif tyrosine phosphorylation on BCR signaling. They further support the idea that CD5 uses mechanisms different from those already described to negatively regulate the BCR pathway.

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^* This work was supported by grants from the Association de la Recherche sur le Cancer and the Ligue Nationale contre le Cancer.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Recipient of a fellowship from the Ministère de la Recherche et de l'Education Nationale.

To whom correspondence should be addressed: CNRS UMR 7627, Centre Hospitalier Pitié-Salpêtrière/CERVI, 83 Blvd de l'Hôpital, 75013, Paris, France. Tel.: 33-1-42177489; Fax: 33-1-42177490; E-mail: gbismuth@ ccr.jussieu.fr.

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Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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