Atypical chemokine receptor 4 shapes activated B cell fate
- Author(s)
- Kara, EE; Bastow, CR; McKenzie, DR; Gregor, CE; Fenix, KA; Babb, R; Norton, TS; Zotos, D; Rodda, LB; Hermes, JR; Bourne, K; Gilchrist, DS; Nibbs, RJ; Alsharifi, M; Vinuesa, CG; Tarlinton, DM; Brink, R; Hill, GR; Cyster, JG; Comerford, I; McColl, SR;
- 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
- Research Division(s)
- Molecular Immunology
- PubMed ID
- 29386231
- Publisher's Version
- https://doi.org/10.1084/jem.20171067
- NHMRC Grants
- NHMRC/1105312,
- Terms of Use/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