Atypical chemokine receptor 4 shapes activated B cell fate

Kara, E. E. et al. (2018) Atypical chemokine receptor 4 shapes activated B cell fate. Journal of Experimental Medicine, 215(3), pp. 801-813. (doi: 10.1084/jem.20171067) (PMID:29386231)

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.

• Item Type: Articles
• Additional Information: This work was supported in part by a grant from the Australian National Health and Medical Research Council (APP1105312) to S.R. McColl, J.G. Cyster, and I. Comerford, J.G. Cyster is an investigator of the Howard Hughes Medical Institute. E.E. Kara is supported by an Australian postgraduate award, a Norman and Patricia Polglase scholarship, and a National Health and Medical Research Council C.J. Martin Overseas Biomedical fellowship.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gilchrist, Dr Derek and Nibbs, Professor Rob
• Authors: Kara, E. E., Bastow, C. R., McKenzie, D. R., Gregor, C. E., Fenix, K. A., Babb, R., Norton, T. S., Zotos, D., Rodda, L. B., Hermes, J. R., Bourne, K., Gilchrist, D. S., Nibbs, R. J., Alsharifi, M., Vinuesa, C. G., Tarlinton, D. M., Brink, R., Hill, G. R., Cyster, J. G., Comerford, I., and McColl, S. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Experimental Medicine
• Publisher: Rockefeller University Press
• ISSN: 0022-1007
• ISSN (Online): 1540-9538
• Copyright Holders: Copyright © 2018 Kara et al.
• First Published: First published in Journal of Experimental Medicine 215:801-813
• Publisher Policy: Reproduced under a Creative Commons License