Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation

Henry J Sutton; Xin Gao; Hannah G Kelly; Brian J Parker; Mariah Lofgren; Cherrelle Dacon; Deepyan Chatterjee; Robert A Seder; Joshua Tan; Azza H Idris; Teresa Neeman; Ian A Cockburn

doi:10.1016/j.immuni.2023.12.010

Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation

Immunity. 2024 Feb 13;57(2):245-255.e5. doi: 10.1016/j.immuni.2023.12.010. Epub 2024 Jan 15.

Authors

Affiliations

¹ Division of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.
² Biological Data Science Institute, The Australian National University, Canberra, ACT 2601, Australia; School of Computing, ANU College of Engineering, Computing & Cybernetics, The Australian National University, Canberra, ACT 2601, Australia.
³ Malaria Unit, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
⁵ Malaria Unit, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA.
⁶ Biological Data Science Institute, The Australian National University, Canberra, ACT 2601, Australia.
⁷ Division of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia. Electronic address: ian.cockburn@anu.edu.au.

PMID: 38228150
PMCID: PMC10922795 (available on 2025-02-13)
DOI: 10.1016/j.immuni.2023.12.010

Abstract

Long-lived plasma cells (PCs) secrete antibodies that can provide sustained immunity against infection. High-affinity cells are proposed to preferentially select into this compartment, potentiating the immune response. We used single-cell RNA-seq to track the germinal center (GC) development of Igh^g2A10 B cells, specific for the Plasmodium falciparum circumsporozoite protein (PfCSP). Following immunization with Plasmodium sporozoites, we identified 3 populations of cells in the GC light zone (LZ). One LZ population expressed a gene signature associated with the initiation of PC differentiation and readily formed PCs in vitro. The estimated affinity of these pre-PC B cells was indistinguishable from that of LZ cells that remained in the GC. This remained true when high- or low-avidity recombinant PfCSP proteins were used as immunogens. These findings suggest that the initiation of PC development occurs via an affinity-independent process.

Keywords: B cells; Plasmodium; affinity maturation; germinal center; plasma cells; single-cell RNA-seq.

MeSH terms

B-Lymphocytes*
Cell Differentiation
Germinal Center*
Plasma Cells
Precursor Cells, B-Lymphoid

Grants and funding

ZIA AI001260/ImNIH/Intramural NIH HHS/United States