Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift

Yang Zhang; Laura Garcia-Ibanez; Carolin Ulbricht; Laurence S C Lok; Jeremy A Pike; Jennifer Mueller-Winkler; Thomas W Dennison; John R Ferdinand; Cameron J M Burnett; Juan C Yam-Puc; Lingling Zhang; Raul Maqueda Alfaro; Yousuke Takahama; Izumi Ohigashi; Geoffrey Brown; Tomohiro Kurosaki; Victor L J Tybulewicz; Antal Rot; Anja Erika Hauser; Menna R Clatworthy; Kai-Michael Toellner

doi:10.1038/s41467-022-29978-y

Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift

Yang Zhang, Laura Garcia-Ibanez, Carolin Ulbricht, Laurence S C Lok, Jeremy A Pike, Jennifer Mueller-Winkler, Thomas W Dennison, John R Ferdinand, Cameron J M Burnett, Juan C Yam-Puc, Lingling Zhang, Raul Maqueda Alfaro, Yousuke Takahama, Izumi Ohigashi, Geoffrey Brown, Tomohiro Kurosaki, Victor L J Tybulewicz, Antal Rot, Anja Erika Hauser, Menna R ClatworthyKai-Michael Toellner

Immunology and Immunotherapy

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Abstract

Infection or vaccination leads to the development of germinal centers (GC) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. Here we follow the migratory pathways of B cells emerging from germinal centers (B EM) and find that many B EM cells migrate into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From the SCS, B EM cells may exit the lymph node to enter distant tissues, while some B EM cells interact with and take up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibits the recycling of B EM cells and results in less efficient adaption to antigenic variation. Our findings thus suggest that the recycling of antigen variant-specific B EM cells and transport of antigen back to GC may support affinity maturation to antigenic drift.

Original language	English
Article number	2460
Number of pages	13
Journal	Nature Communications
Volume	13
Issue number	1
Early online date	5 May 2022
DOIs	https://doi.org/10.1038/s41467-022-29978-y
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
Y.Z., C.J.M.B., J.C.Y.P., and K.M.T. were funded by the BBSRC (BB/S003800/1, BB/M025292/1) and MRC (MR/P001874/1). L.G.I. and G.B. were supported by EU Marie Curie Initial Training Network DECIDE. V.L.J.T. was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001194), the UK Medical Research Council (FC001194), and the Wellcome Trust (FC001194). For the purpose of Open Access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission. MRC is supported by a Medical Research Council New Investigator Research Grant (MR/N024907/1), a Chan-Zuckerberg Initiative Human Cell Atlas Technology Development Grant, a Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002). A.E.H. was supported by Deutsche Forschungsgemeinschaft (DFG) TRR130, TP17 and C01, and DFG HA5354/10-1. The authors would like to acknowledge the Flow Cytometry Platform, University of Birmingham for support of flow cytometry experiments.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Antigenic Drift and Shift
B-Lymphocytes
Germinal Center
Lymph Nodes
Memory B Cells

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-022-29978-yLicence: Creative Commons: Attribution (CC BY)

ZhangY2022RecyclingFinal published version, 8.32 MBLicence: Creative Commons: Attribution (CC BY)

Role of memory B cell migration through the lymph node subcapsular sinus
Zhang, Y., Toellner, K. & Long, H.
Biotechnology & Biological Sciences Research Council
1/11/19 → 28/02/23
Project: Research Councils
Determining the potential universal applicability of a diurnal response to vaccination and the associated circadian immune processes
Lord, J., Richter, A., Drayson, M. & Toellner, K.
Medical Research Council
1/01/17 → 31/03/21
Project: Research Councils

Cite this

Zhang, Y., Garcia-Ibanez, L., Ulbricht, C., Lok, L. S. C., Pike, J. A., Mueller-Winkler, J., Dennison, T. W., Ferdinand, J. R., Burnett, C. J. M., Yam-Puc, J. C., Zhang, L., Alfaro, R. M., Takahama, Y., Ohigashi, I., Brown, G., Kurosaki, T., Tybulewicz, V. L. J., Rot, A., Hauser, A. E., ... Toellner, K.-M. (2022). Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift. Nature Communications, 13(1), Article 2460. https://doi.org/10.1038/s41467-022-29978-y

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title = "Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift",

abstract = "Infection or vaccination leads to the development of germinal centers (GC) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. Here we follow the migratory pathways of B cells emerging from germinal centers (B EM) and find that many B EM cells migrate into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From the SCS, B EM cells may exit the lymph node to enter distant tissues, while some B EM cells interact with and take up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibits the recycling of B EM cells and results in less efficient adaption to antigenic variation. Our findings thus suggest that the recycling of antigen variant-specific B EM cells and transport of antigen back to GC may support affinity maturation to antigenic drift. ",

keywords = "Antigenic Drift and Shift, B-Lymphocytes, Germinal Center, Lymph Nodes, Memory B Cells",

author = "Yang Zhang and Laura Garcia-Ibanez and Carolin Ulbricht and Lok, {Laurence S C} and Pike, {Jeremy A} and Jennifer Mueller-Winkler and Dennison, {Thomas W} and Ferdinand, {John R} and Burnett, {Cameron J M} and Yam-Puc, {Juan C} and Lingling Zhang and Alfaro, {Raul Maqueda} and Yousuke Takahama and Izumi Ohigashi and Geoffrey Brown and Tomohiro Kurosaki and Tybulewicz, {Victor L J} and Antal Rot and Hauser, {Anja Erika} and Clatworthy, {Menna R} and Kai-Michael Toellner",

note = "Funding Information: Y.Z., C.J.M.B., J.C.Y.P., and K.M.T. were funded by the BBSRC (BB/S003800/1, BB/M025292/1) and MRC (MR/P001874/1). L.G.I. and G.B. were supported by EU Marie Curie Initial Training Network DECIDE. V.L.J.T. was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001194), the UK Medical Research Council (FC001194), and the Wellcome Trust (FC001194). For the purpose of Open Access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission. MRC is supported by a Medical Research Council New Investigator Research Grant (MR/N024907/1), a Chan-Zuckerberg Initiative Human Cell Atlas Technology Development Grant, a Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002). A.E.H. was supported by Deutsche Forschungsgemeinschaft (DFG) TRR130, TP17 and C01, and DFG HA5354/10-1. The authors would like to acknowledge the Flow Cytometry Platform, University of Birmingham for support of flow cytometry experiments. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-29978-y",

language = "English",

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Zhang, Y, Garcia-Ibanez, L, Ulbricht, C, Lok, LSC, Pike, JA, Mueller-Winkler, J, Dennison, TW, Ferdinand, JR, Burnett, CJM, Yam-Puc, JC, Zhang, L, Alfaro, RM, Takahama, Y, Ohigashi, I, Brown, G, Kurosaki, T, Tybulewicz, VLJ, Rot, A, Hauser, AE, Clatworthy, MR & Toellner, K-M 2022, 'Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift', Nature Communications, vol. 13, no. 1, 2460. https://doi.org/10.1038/s41467-022-29978-y

TY - JOUR

T1 - Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift

AU - Zhang, Yang

AU - Garcia-Ibanez, Laura

AU - Ulbricht, Carolin

AU - Lok, Laurence S C

AU - Pike, Jeremy A

AU - Mueller-Winkler, Jennifer

AU - Dennison, Thomas W

AU - Ferdinand, John R

AU - Burnett, Cameron J M

AU - Yam-Puc, Juan C

AU - Zhang, Lingling

AU - Alfaro, Raul Maqueda

AU - Takahama, Yousuke

AU - Ohigashi, Izumi

AU - Brown, Geoffrey

AU - Kurosaki, Tomohiro

AU - Tybulewicz, Victor L J

AU - Rot, Antal

AU - Hauser, Anja Erika

AU - Clatworthy, Menna R

AU - Toellner, Kai-Michael

N1 - Funding Information: Y.Z., C.J.M.B., J.C.Y.P., and K.M.T. were funded by the BBSRC (BB/S003800/1, BB/M025292/1) and MRC (MR/P001874/1). L.G.I. and G.B. were supported by EU Marie Curie Initial Training Network DECIDE. V.L.J.T. was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001194), the UK Medical Research Council (FC001194), and the Wellcome Trust (FC001194). For the purpose of Open Access, the author has applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission. MRC is supported by a Medical Research Council New Investigator Research Grant (MR/N024907/1), a Chan-Zuckerberg Initiative Human Cell Atlas Technology Development Grant, a Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002). A.E.H. was supported by Deutsche Forschungsgemeinschaft (DFG) TRR130, TP17 and C01, and DFG HA5354/10-1. The authors would like to acknowledge the Flow Cytometry Platform, University of Birmingham for support of flow cytometry experiments. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Infection or vaccination leads to the development of germinal centers (GC) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. Here we follow the migratory pathways of B cells emerging from germinal centers (B EM) and find that many B EM cells migrate into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From the SCS, B EM cells may exit the lymph node to enter distant tissues, while some B EM cells interact with and take up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibits the recycling of B EM cells and results in less efficient adaption to antigenic variation. Our findings thus suggest that the recycling of antigen variant-specific B EM cells and transport of antigen back to GC may support affinity maturation to antigenic drift.

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KW - B-Lymphocytes

KW - Germinal Center

KW - Lymph Nodes

KW - Memory B Cells

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DO - 10.1038/s41467-022-29978-y

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JO - Nature Communications

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Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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Projects

Role of memory B cell migration through the lymph node subcapsular sinus

Determining the potential universal applicability of a diurnal response to vaccination and the associated circadian immune processes

Cite this