Atypical chemokine receptor 4 shapes activated B cell fate

Ervin E. Kara, Cameron R. Bastow, Duncan R. McKenzie, Carly E. Gregor, Kevin A. Fenix, Rachelle Babb, Todd S. Norton, Dimitra Zotos, Lauren B. Rodda, Jana R. Hermes, Katherine Bourne, Derek S. Gilchrist, Robert J. Nibbs, Mohammed Alsharifi, Carola G. Vinuesa, David M. Tarlinton, Robert Brink, Geoffrey R. Hill, Jason G. Cyster, Iain Comerford & 1 others Shaun R. McColl

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)801-813
Number of pages13
JournalJournal of Experimental Medicine
Volume215
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Cite this

Kara, E. E., Bastow, C. R., McKenzie, D. R., Gregor, C. E., Fenix, K. A., Babb, R., ... McColl, S. R. (2018). Atypical chemokine receptor 4 shapes activated B cell fate. Journal of Experimental Medicine, 215(3), 801-813. https://doi.org/10.1084/jem.20171067
Kara, Ervin E. ; Bastow, Cameron R. ; McKenzie, Duncan R. ; Gregor, Carly E. ; Fenix, Kevin A. ; Babb, Rachelle ; Norton, Todd S. ; Zotos, Dimitra ; Rodda, Lauren B. ; Hermes, Jana R. ; Bourne, Katherine ; Gilchrist, Derek S. ; Nibbs, Robert J. ; Alsharifi, Mohammed ; Vinuesa, Carola G. ; Tarlinton, David M. ; Brink, Robert ; Hill, Geoffrey R. ; Cyster, Jason G. ; Comerford, Iain ; McColl, Shaun R. / Atypical chemokine receptor 4 shapes activated B cell fate. In: Journal of Experimental Medicine. 2018 ; Vol. 215, No. 3. pp. 801-813.
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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.",
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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 2018, 'Atypical chemokine receptor 4 shapes activated B cell fate', Journal of Experimental Medicine, vol. 215, no. 3, pp. 801-813. https://doi.org/10.1084/jem.20171067

Atypical chemokine receptor 4 shapes activated B cell fate. / Kara, Ervin E.; Bastow, Cameron R.; McKenzie, Duncan R.; Gregor, Carly E.; Fenix, Kevin A.; Babb, Rachelle; Norton, Todd S.; Zotos, Dimitra; Rodda, Lauren B.; Hermes, Jana R.; Bourne, Katherine; Gilchrist, Derek S.; Nibbs, Robert J.; Alsharifi, Mohammed; Vinuesa, Carola G.; Tarlinton, David M.; Brink, Robert; Hill, Geoffrey R.; Cyster, Jason G.; Comerford, Iain; McColl, Shaun R.

In: Journal of Experimental Medicine, Vol. 215, No. 3, 01.03.2018, p. 801-813.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Kara, Ervin E.

AU - Bastow, Cameron R.

AU - McKenzie, Duncan R.

AU - Gregor, Carly E.

AU - Fenix, Kevin A.

AU - Babb, Rachelle

AU - Norton, Todd S.

AU - Zotos, Dimitra

AU - Rodda, Lauren B.

AU - Hermes, Jana R.

AU - Bourne, Katherine

AU - Gilchrist, Derek S.

AU - Nibbs, Robert J.

AU - Alsharifi, Mohammed

AU - Vinuesa, Carola G.

AU - Tarlinton, David M.

AU - Brink, Robert

AU - Hill, Geoffrey R.

AU - Cyster, Jason G.

AU - Comerford, Iain

AU - McColl, Shaun R.

PY - 2018/3/1

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N2 - 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.

AB - 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.

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U2 - 10.1084/jem.20171067

DO - 10.1084/jem.20171067

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JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

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Kara EE, Bastow CR, McKenzie DR, Gregor CE, Fenix KA, Babb R et al. Atypical chemokine receptor 4 shapes activated B cell fate. Journal of Experimental Medicine. 2018 Mar 1;215(3):801-813. https://doi.org/10.1084/jem.20171067