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 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.
|ISBN||1540-9538 (Electronic) 0022-1007 (Linking)|
|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.; McColl, S. R.|
|Responsible Garvan Author||Prof Robert Brink|
|Publisher Name||JOURNAL OF EXPERIMENTAL MEDICINE|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/29386231|