Atypical chemokine receptor 4 shapes activated B cell fate
| Autor: | Ervin E. Kara, Dimitra Zotos, Katherine Bourne, David M. Tarlinton, Duncan R. McKenzie, Cameron R. Bastow, Geoffrey R. Hill, Shaun R. McColl, Jason G. Cyster, Robert Brink, Kevin A. Fenix, Derek S. Gilchrist, Rachelle Babb, Iain Comerford, Jana R. Hermes, Carly E. Gregor, Todd Norton, Carola G. Vinuesa, Robert J. B. Nibbs, Mohammed Alsharifi, Lauren B. Rodda |
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| Přispěvatelé: | Kara, Ervin E, Bastow, Cameron R, McKenzie, Duncan R, Gregor, Carly E, McColl, Shaun R |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Immunology C-C chemokine receptor type 7 Inbred C57BL Medical and Health Sciences Mice Receptors CCR 03 medical and health sciences Chemokine receptor Atypical Chemokine Receptor 4 Receptors medicine Animals Immunology and Allergy Cell Lineage Antigens Receptor Research Articles B cell Cell Proliferation B-Lymphocytes Chemistry CCL19 Brief Definitive Report Germinal center atypical chemokine receptor 4 Germinal Center CCR Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Spleen CCL21 |
| Zdroj: | The Journal of Experimental Medicine The Journal of experimental medicine, vol 215, iss 3 |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Kara et al. show that ACKR4 regulates early activated B cell differentiation fate. ACKR4 limits the early proliferation of activated B cells by restricting their initial access to the splenic interfollicular zone. 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. |
| Databáze: | OpenAIRE |
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