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  MIF Promotes B Cell Chemotaxis through the Receptors CXCR4 and CD74 and ZAP-70 Signaling

Klasen, C., Ohl, K., Sternkopf, M., Shachar, I., Schmitz, C., Heussen, N., et al. (2014). MIF Promotes B Cell Chemotaxis through the Receptors CXCR4 and CD74 and ZAP-70 Signaling. The Journal of Immunology, 192, 5273-5284.

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Klasen, Christina, Autor
Ohl, Kim, Autor
Sternkopf, Marieke, Autor
Shachar, Idit, Autor
Schmitz, Corinna, Autor
Heussen, Nicole, Autor
Hobeika, Elias1, Autor           
Levit-Zerdoun, Ella2, Autor
Tenbrock, Klaus, Autor
Reth, Michael1, Autor           
Bernhagen, Jürgen, Autor
El Bounkari, Omar, Autor
Affiliations:
1Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243645              
2Max Planck Society, ou_persistent13              

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 Zusammenfassung: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with chemokine-like functions that plays a pivotal role in the pathogenesis of inflammatory diseases by promoting leukocyte recruitment. We showed that MIF promotes the atherogenic recruitment of monocytes and T cells through its receptors CXCR2 and CXCR4. Effects of MIF on B cell recruitment have not been addressed. In this study, we tested the involvement of MIF in B cell chemotaxis and studied the underlying mechanism. We show that MIF promotes primary murine B cell chemotaxis in a dose-dependent manner, comparable to the B cell chemokines CXCL13 and CXCL12. Splenic B cells express CXCR4 and the receptor CD74 but not CXCR2. Inhibition of CXCR4 or CD74 or a genetic deficiency of Cd74 in primary B cells fully abrogated MIF-mediated B cell migration, implying cooperative involvement of both receptors. MIF stimulation of B cells resulted in a rapid increase in intracellular Ca2+ mobilization and F-actin polymerization. Intriguingly, the tyrosine kinase ZAP-70 was activated upon MIF and CXCL12 treatment in a CXCR4- and CD74-dependent manner. Pharmacological inhibition of ZAP-70 resulted in abrogation of primary B cell migration. Functional involvement of ZAP-70 was confirmed by small interfering RNA-mediated knockdown in Ramos B cell migration. Finally, primary B cells from ZAP-70 gene-deficient mice exhibited ablated transmigration in response to MIF or CXCL12. We conclude that MIF promotes the migration of B cells through a ZAP-70-dependent pathway mediated by cooperative engagement of CXCR4 and CD74. The data also suggest that MIF may contribute to B cell recruitment in vivo (e.g., in B cell-related immune disorders).

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Sprache(n): eng - English
 Datum: 2014
 Publikationsstatus: Erschienen
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 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: eDoc: 701185
 Art des Abschluß: -

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Titel: The Journal of Immunology
  Alternativer Titel : J. Immunol.
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 192 Artikelnummer: - Start- / Endseite: 5273 - 5284 Identifikator: -