期刊
FASEB JOURNAL
卷 26, 期 12, 页码 4841-4854出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.12-208876
关键词
modulation of the B-cell response; binding affinity; G alpha(i) activation
资金
- Spanish Ministry of Science and Innovation [SAF 2008-03388, SAF 2011-27370, MTM2010-17366]
- RETICS Program [RD08/0075/0010]
- Instituto de Salud Carlos III, Centro de Investigacion Biomedica en Red de Salud Mental
- Basque Government [GIC10/147]
- European Union [223404]
B-cell movement into lymphoid follicles depends on the expression of the chemokine receptor CXCR5 and the recently reported Epstein-Barr virus-induced receptor 2 (EBI2). In cooperation with CXCR5, EBI2 helps to position activated B cells in the follicle, although the mechanism is poorly understood. Using human HEK293T cells and fluorescence resonance energy transfer (FRET) techniques, we demonstrate that CXCR5 and EBI2 form homo- and heterodimers. EBI2 expression modulated CXCR5 homodimeric complexes, as indicated by the FRET50 value (CXCR5 homodimer, 0.9851 +/- 0.0784; CXCR5 homodimer+EBI2, 1.7320 +/- 0.4905; P<0.05). HEK293T cells expressing CXCR5/EBI2 and primary activated murine B cells both down-modulated CXCR5-mediated responses, such as Ca2+ flux, cell migration, and MAPK activation; this modulation did not occur when primary B cells were obtained from EBI2(-/-) mice. The mechanism involves a reduction in binding affinity of the ligand (CXCL13) for CXCR5 (K-D: 5.05 x 10(-8) M for CXCR5 alone vs. 1.49 x 10(-7) M for CXCR5/EBI2) and in the efficacy (E-max) of G-protein activation in CXCR5/EBI2-coexpressing cells (42.33 +/- 4.3%; P<0.05). These findings identify CXCR5/EBI2 heterodimers as functional units that contribute to the plasticity of CXCL13-mediated B-cell responses.-Barroso, R., Munoz, L. Martinez., Barrondo, S., Vega, B., Holgado, B. L., Lucas, P., Baillo, A., Salles, J., Rodriguez-Frade J. M., Mellado, M. EBI2 regulates CXCL13-mediated responses by heterodimerization with CXCR5. FASEB J. 26, 4841-4854 (2012). www.fasebj.org
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