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Heterogeneity of phenotype and function reflects the multistage development of t follicular helper cells

Trüb, Marta; Barr, Tom A.; Morrison, Vicky L.; Brown, Sheila; Caserta, Stefano; Rixon, Jordan; Ivens, Alasdair; Gray, David

Authors

Marta Trüb

Tom A. Barr

Vicky L. Morrison

Sheila Brown

Jordan Rixon

Alasdair Ivens

David Gray



Abstract

T follicular helper cells (Tfh) provide crucial signals for germinal center (GC) formation, but Tfh populations are heterogeneous. While PD1 hi Tfh are important in the GC response, the function of the PD1 lo Tfh-like subset is unknown. We show that these cells, like the PD1 hi GC-Tfh, depend upon B cells; however, their entry to follicles is independent of CXCR5 or cognate interactions with B cells. The differentiation into PD1 hi Tfh is dependent on MHC class II interactions with B cells and requires CXCR5. Our data suggest a Tfh differentiation pathway that is initially B cell-independent, then dependent on non-cognate B cell interactions, and finally following cognate interaction with B cells and CXCR5-ligands allows the formation of GC-Tfh. The PD1 lo Tfh-like cells make early cytokine responses and may represent precursors of CD4 memory cells.

Journal Article Type Article
Publication Date Apr 28, 2017
Journal Frontiers in Immunology
Electronic ISSN 1664-3224
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 8
Issue APR
Pages 489
APA6 Citation Trüb, M., Barr, T. A., Morrison, V. L., Brown, S., Caserta, S., Rixon, J., …Gray, D. (2017). Heterogeneity of phenotype and function reflects the multistage development of t follicular helper cells. Frontiers in immunology, 8(APR), 489. https://doi.org/10.3389/fimmu.2017.00489
DOI https://doi.org/10.3389/fimmu.2017.00489
Keywords T follicular helper cells; T cell memory; T follicular helper cell subsets; Germinal centres; T cell heterogeneity
Publisher URL https://www.frontiersin.org/articles/10.3389/fimmu.2017.00489/full
Related Public URLs http://sro.sussex.ac.uk/61764/
Copyright Statement © 2017 Trüb, Barr, Morrison, Brown, Caserta, Rixon, Ivens and Gray. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Copyright Statement
© 2017 Trüb, Barr, Morrison, Brown, Caserta, Rixon, Ivens and Gray. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.



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