B cell dissemination patterns during the germinal center reaction revealed by whole-organ imaging

Liat Stoler-Barak, Adi Biram, Natalia Davidzohn, Yoseph Addadi, Ofra Golani, Ziv Shulman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Germinal centers (GCs) are sites wherein B cells proliferate and mutate their immunoglobulins in the dark zone (DZ), followed by affinity-based selection in the light zone (LZ). Here, we mapped the location of single B cells in the context of intact lymph nodes (LNs) throughout the GC response, and examined the role of BCR affinity in dictating their position. Imaging of entire GC structures and proximal single cells by light-sheet fluorescence microscopy revealed that individual B cells that previously expressed AID are located within the LN cortex, in an area close to the GC LZ. Using in situ photoactivation, we demonstrated that B cells migrate from the LZ toward the GC outskirts, while DZ B cells are confined to the GC. B cells expressing very-low-affinity BCRs formed GCs but were unable to efficiently disperse within the follicles. Our findings reveal that BCR affinity regulates B cell positioning during the GC response.

Original languageEnglish
Pages (from-to)2515-2530
Number of pages16
JournalJournal of Experimental Medicine
Volume216
Issue number11
Early online date12 Jun 2019
DOIs
Publication statusPublished - Nov 2019

Funding

Funding Information: Z. Shulman is supported by the European Research Council grant no. 677713 and the Israel Science Foundation (2759/19). Z. Shulman is a European Molecular Biology Organization Young Investigator and is also supported by the Human Frontiers of Science Program (CDA-00023/2016), the Azrieli Foundation, the Rising Tide Foundation, the Morris Kahn Institute for Human Immunology, and grants from the Moross Integrated Cancer Center, the Comisaroff Family Trust, the Irma & Jacques Ber-Lehmsdorf Foundation, the Gerald O. Mann Charitable Foundation, and the David M. Polen Charitable Trust. Imaging was made possible thanks to “The de Picciotto-Lesser Cell Observatory in memory of Wolf and Ruth Lesser.” The authors declare no competing financial interests. Author contributions: L. Stoler-Barak designed and conducted the experiments, performed data analysis, and wrote the manuscript. A. Biram and N. Davidzohn performed animal-related procedures. Y. Addadi assisted with light sheet imaging. O. Golani created the image quantification pipeline. Z. Shulman designed experiments, supervised the study, and wrote the manuscript. Publisher Copyright: © 2019 Stoler-Barak et al. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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