Atypical chemokine receptor 4 shapes activated B cell fate

Activated B cells can initially differentiate into three functionally distinct fates—early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells—by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and d...

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Detalles Bibliográficos
Autores principales: Kara, Ervin E., Bastow, Cameron R., McKenzie, Duncan R., Gregor, Carly E., Fenix, Kevin A., Babb, Rachelle, Norton, Todd S., Zotos, Dimitra, Rodda, Lauren B., Hermes, Jana R., Bourne, Katherine, Gilchrist, Derek S., Nibbs, Robert J., Alsharifi, Mohammed, Vinuesa, Carola G., Tarlinton, David M., Brink, Robert, Hill, Geoffrey R., Cyster, Jason G., Comerford, Iain, McColl, Shaun R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839757/
https://www.ncbi.nlm.nih.gov/pubmed/29386231
http://dx.doi.org/10.1084/jem.20171067
Descripción
Sumario:Activated B cells can initially differentiate into three functionally distinct fates—early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells—by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation. Consequently, ACKR4 deficiency enhanced early PB and GC B cell responses in a CCL19/CCL21-dependent and B cell–intrinsic manner. Conversely, aberrant localization of ACKR4-deficient activated B cells to the IFZ was associated with their preferential commitment to the early PB linage. Our results reveal a regulatory mechanism of B cell trafficking via an atypical chemokine receptor that shapes activated B cell fate.

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