CCR6 Defines Memory B Cell Precursors in Mouse and Human Germinal Centers, Revealing Light-Zone Location and Predominant Low Antigen Affinity

Dan Suan; Nike J Kräutler; Jesper L V Maag; Danyal Butt; Katherine Bourne; Jana R Hermes; Danielle T Avery; Clara Young; Aaron Statham; Michael Elliott; Marcel E Dinger; Antony Basten; Stuart G Tangye; Robert Brink

doi:10.1016/j.immuni.2017.11.022

CCR6 Defines Memory B Cell Precursors in Mouse and Human Germinal Centers, Revealing Light-Zone Location and Predominant Low Antigen Affinity

Immunity. 2017 Dec 19;47(6):1142-1153.e4. doi: 10.1016/j.immuni.2017.11.022.

Authors

Affiliations

¹ Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; Westmead Clinical School, University of Sydney, Sydney, NSW 2145, Australia.
² Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
³ Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
⁴ Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
⁵ Central Clinical School, University of Sydney, Camperdown, NSW 2006, Australia.
⁶ Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, UNSW Sydney, Darlinghurst, NSW 2010, Australia.
⁷ Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, UNSW Sydney, Darlinghurst, NSW 2010, Australia.
⁸ Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, UNSW Sydney, Darlinghurst, NSW 2010, Australia. Electronic address: r.brink@garvan.org.au.

PMID: 29262350
DOI: 10.1016/j.immuni.2017.11.022

Abstract

Memory B cells (MBCs) and plasma cells (PCs) constitute the two cellular outputs of germinal center (GC) responses that together facilitate long-term humoral immunity. Although expression of the transcription factor BLIMP-1 identifies cells undergoing PC differentiation, no such marker exists for cells committed to the MBC lineage. Here, we report that the chemokine receptor CCR6 uniquely marks MBC precursors in both mouse and human GCs. CCR6⁺ GC B cells were highly enriched within the GC light zone (LZ), were the most quiescent of all GC B cells, exhibited a cell-surface phenotype and gene expression signature indicative of an MBC transition, and possessed the augmented response characteristics of MBCs. MBC precursors within the GC LZ predominantly possessed a low affinity for antigen but also included cells from within the high-affinity pool. These data indicate a fundamental dichotomy between the processes that drive MBC and PC differentiation during GC responses.

Keywords: B cell memory; CCR6; antigen affinity; germinal center.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
B7-2 Antigen / genetics
B7-2 Antigen / immunology
Cell Differentiation
Cell Lineage / immunology
Gene Expression Profiling
Gene Expression Regulation
Germinal Center / cytology
Germinal Center / immunology*
Humans
Immunity, Humoral*
Immunologic Memory
Immunophenotyping
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phenotype
Plasma Cells / cytology
Plasma Cells / immunology*
Positive Regulatory Domain I-Binding Factor 1 / genetics
Positive Regulatory Domain I-Binding Factor 1 / immunology
Precursor Cells, B-Lymphoid / cytology
Precursor Cells, B-Lymphoid / immunology*
Receptors, CCR6 / genetics
Receptors, CCR6 / immunology*
Receptors, CXCR4 / genetics
Receptors, CXCR4 / immunology
Signal Transduction

Substances

B7-2 Antigen
CCR6 protein, mouse
CXCR4 protein, mouse
Cd86 protein, mouse
Prdm1 protein, mouse
Receptors, CCR6
Receptors, CXCR4
Positive Regulatory Domain I-Binding Factor 1