EBI2 regulates CXCL13-mediated responses by heterodimerization with CXCR5
Rubén Barroso1, Laura Martínez Muñoz, Sergio Barrondo
1Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.
Summary
Epstein-Barr virus-induced receptor 2 (EBI2) and CXCR5 form dimers, modulating B-cell responses. This interaction alters chemokine binding and signaling, impacting B-cell positioning within lymphoid follicles.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- B-cell homing to lymphoid follicles is crucial for immune responses.
- Chemokine receptor CXCR5 and Epstein-Barr virus-induced receptor 2 (EBI2) are key regulators of B-cell localization.
- The precise mechanism by which EBI2 cooperates with CXCR5 remains unclear.
Purpose of the Study:
- To investigate the molecular interactions between CXCR5 and EBI2.
- To elucidate the functional consequences of CXCR5-EBI2 complex formation on B-cell responses.
- To understand the impact on CXCL13-mediated signaling pathways.
Main Methods:
- Utilized human HEK293T cells and fluorescence resonance energy transfer (FRET) techniques.
- Analyzed homo- and heterodimerization of CXCR5 and EBI2.
- Assessed CXCR5-mediated responses including calcium (Ca2+) flux, cell migration, and MAPK activation in primary murine B cells.
Main Results:
- Demonstrated that CXCR5 and EBI2 form both homo- and heterodimers.
- Showed that EBI2 expression significantly modulated CXCR5 homodimeric complexes.
- Observed down-modulation of CXCR5-mediated responses in cells coexpressing CXCR5 and EBI2, linked to reduced CXCL13 binding affinity and G-protein activation efficacy.
- Confirmed these effects were dependent on EBI2 expression, as they were absent in EBI2(-/-) B cells.
Conclusions:
- CXCR5 and EBI2 form functional heterodimers that influence B-cell localization.
- These heterodimers contribute to the plasticity of B-cell responses mediated by CXCL13.
- Identified a novel mechanism regulating B-cell positioning within lymphoid follicles.
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