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; Shaun R. McColl

doi:10.1084/jem.20171067

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^*Shaun R. McColl

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

19 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 language	English
Pages (from-to)	801-813
Number of pages	13
Journal	Journal of Experimental Medicine
Volume	215
Issue number	3
DOIs	https://doi.org/10.1084/jem.20171067
Publication status	Published - 1 Mar 2018

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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., ... 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

@article{3ecc3ebe2208425ebe7ac93eb9d28b8e,

title = "Atypical chemokine receptor 4 shapes activated B cell fate",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2018 Kara et al.",

year = "2018",

month = mar,

day = "1",

doi = "10.1084/jem.20171067",

language = "English",

volume = "215",

pages = "801--813",

journal = "Journal of Experimental Medicine",

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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

TY - JOUR

T1 - Atypical chemokine receptor 4 shapes activated B cell fate

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

Y1 - 2018/3/1

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

M3 - Article

SN - 0022-1007

VL - 215

SP - 801

EP - 813

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 3

ER -

Atypical chemokine receptor 4 shapes activated B cell fate

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