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 Blood, 1 March 2008, Vol. 111, No. 5, pp. 2744-2754.
Prepublished online as a Blood First Edition Paper on January 2, 2008; DOI 10.1182/blood-2007-03-081232.

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IMMUNOBIOLOGY

BAFF enhances chemotaxis of primary human B cells: a particular synergy between BAFF and CXCL13 on memory B cells

Gamal Badr1, Gwenoline Borhis1, Eric A. Lefevre2, Nada Chaoul1, Frederique Deshayes3, Valérie Dessirier4, Genevieve Lapree4, Andreas Tsapis4, and Yolande Richard1

1 Service of Immuno-Virology, Commissariat à l'Energie Atomique, Departement des Sciences du Vivant, Institut des maladies émergentes et therapies innovantes, Unité Mixte de Recherche (UMR)-E1, Université Paris-Sud, Orsay, France; 2 Compton Laboratory, Institute for Animal Health, Compton, United Kingdom; 3 UMR-Centre National de la Recherche Scientifique 7592, Paris, France; and 4 Inserm U841 Team 2, Creteil, France

B-cell–activating factor of the TNF family, (BAFF), and a proliferation-inducing ligand (APRIL) regulate B-lymphocyte survival and activation. We report that BAFF, but not APRIL, increased the chemotactic response of primary human B cells to CCL21, CXCL12, and CXCL13. The BAFF-induced increase in B-cell chemotaxis was totally abolished by blockade of BAFF-R and was strongly dependent on the activation of PI3K/AKT, NF-{kappa}B, and p38MAPK pathways. BAFF had similar effects on the chemotaxis of naive and memory B cells in response to CCL21 but increased more strongly that of memory B cells to CXCL13 than that of naive B cells. Our findings indicate a previously unreported role for the BAFF/BAFF-R pair in mature B-cell chemotaxis. The synergy between CXCL13 and BAFF produced by stromal cells and follicular dendritic cells may have important implications for B-cell homeostasis, the development of normal B-cell areas, and for the formation of germinal center–like follicles that may be observed in various autoimmune diseases.


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