Atypical chemokine receptor 4 shapes activated B cell fate
Journal Title
J Exp Med
Publication Type
Journal Article in press
Abstract
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.
Publisher
Rockefeller Press
WEHI Research Division(s)
Molecular Immunology
PubMed ID
29386231
NHMRC Grants
NHMRC/1105312
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-02-28 08:04:57
Last Modified: 2018-02-28 08:31:35
An error has occurred. This application may no longer respond until reloaded. Reload 🗙