Regulation of activated B cell differentiation by atypical chemokine receptor 4 — ASN Events
  1. Schedule
  2. Workshop 5: Lymphocyte biology 2
  3. Regulation of activated B cell differentiation by atypical chemokine receptor 4

Regulation of activated B cell differentiation by atypical chemokine receptor 4 (#61)

Ervin E Kara 1 2 , Cameron R Bastow 1 , Duncan R McKenzie 1 3 , Carly E Gregor 1 , Kevin Aaron Fenix 1 , Todd S Norton 1 , Jason G Cyster 4 , Shaun R McColl 1 , Iain Comerford 1
  1. University of Adelaide, Adelaide, SA, Australia
  2. Rockefeller University, New York, NY, USA
  3. Francis Crick Institute, London, UK
  4. Howard Hughes Medical Istitute, San Francisco, California, USA

Upon activation, B cells dynamically regulate chemoattractant responsiveness enabling spatio-temporal access to distinct lymphoid niches that drive their proliferation and differentiation. Activated B cells can initially differentiate into three functionally-distinct fates: early plasmablasts (PB), germinal center B (GCB) or early memory B (EBM) cells by mechanisms that remain ill-defined. Here, we identify a new modality of B cell migration that shapes fate trifurcation of activated B cells via atypical chemokine receptor 4 (ACKR4), a scavenger of CCR7 ligand chemokines CCL19/CCL21. By restricting initial access to the splenic interfollicular zone (IFZ), ACKR4 limits early proliferation of activated B cells, reducing the frequency of these cells available for subsequent differentiation. Consequently, ACKR4-deficiency enhanced early PB, GCB and EBM cell development in a CCL19/CCL21-dependent and B cell-intrinsic manner. Additionally, aberrant localization to the IFZ by ACKR4-deficient activated B cells enhanced interferon regulatory factor 4 (IRF4) expression guiding their preferential commitment to the early PB lineage. Our results reveal a previously unrecognized regulatory mechanism of B cell trafficking via an atypical chemokine receptor that governs activated B cell differentiation and fate.​

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