Guidance of B cells by the orphan G protein-coupled receptor EBI2 shapes humoral immune responses.
Humoral immunity depends on both rapid and long-term antibody production against invading pathogens. This is achieved by the generation of spatially distinct extrafollicular plasmablast and follicular germinal center (GC) B cell populations, but the signals that guide responding B cells to these alternative compartments have not been fully elucidated. Here, we show that expression of the orphan G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) by activated B cells was essential for their movement to extrafollicular sites and induction of early plasmablast responses. Conversely, downregulation of EBI2 enabled B cells to access the center of follicles and promoted efficient GC formation. EBI2 therefore provides a previously uncharacterized dimension to B cell migration that is crucial for coordinating rapid versus long-term antibody responses.
Gatto
Dominique
D
Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia. d.gatto@garvan.org.au
Paus
Didrik
D
Basten
Antony
A
Mackay
Charles R
CR
Brink
Robert
R
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; C543809:Gpr183 protein, mouse; D043562:Receptors, G-Protein-Coupled