BAFF enhances chemotaxis of primary human B cells: a particular synergy between BAFF and CXCL13 on memory B cells.
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-kappaB, 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.
Badr
Gamal
G
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-E1, Université Paris-Sud, Orsay, France.
Borhis
Gwenoline
G
Lefevre
Eric A
EA
Chaoul
Nada
N
Deshayes
Frederique
F
Dessirier
Valérie
V
Lapree
Genevieve
G
Tsapis
Andreas
A
Richard
Yolande
Y
D053264:B-Cell Activating Factor / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000276:immunology*; D002633:Chemotaxis; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007156:Immunologic Memory; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D009500:Neutralization Tests; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D054382:Chemokine CXCL13; D020672:I-kappa B Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D048051:p38 Mitogen-Activated Protein Kinases; D054460:rho-Associated Kinases; C110663:CXCL13 protein, human; C000606204:NFKBIA protein, human; C114631:TNFSF13 protein, human