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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Citations (SciVal)

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.

Original language	English
Pages (from-to)	245-255.e5
Number of pages	17
Journal	Immunity
Volume	57
Issue number	2
Early online date	15 Jan 2024
DOIs	https://doi.org/10.1016/j.immuni.2023.12.010
Publication status	Published - 13 Feb 2024

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10.1016/j.immuni.2023.12.010

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@article{aae8490cb0b04327a2bfbdd0543c56b7,

title = "Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation",

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 Ighg2A10 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",

author = "Sutton, \{Henry J.\} and Xin Gao and Kelly, \{Hannah G.\} and Parker, \{Brian J.\} and Mariah Lofgren and Cherrelle Dacon and Deepyan Chatterjee and Seder, \{Robert A.\} and Joshua Tan and Idris, \{Azza H.\} and Teresa Neeman and Cockburn, \{Ian A.\}",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2024",

month = feb,

day = "13",

doi = "10.1016/j.immuni.2023.12.010",

language = "English",

volume = "57",

pages = "245--255.e5",

journal = "Immunity",

issn = "1074-7613",

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T1 - Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation

AU - Sutton, Henry J.

AU - Gao, Xin

AU - Kelly, Hannah G.

AU - Parker, Brian J.

AU - Lofgren, Mariah

AU - Dacon, Cherrelle

AU - Chatterjee, Deepyan

AU - Seder, Robert A.

AU - Tan, Joshua

AU - Idris, Azza H.

AU - Neeman, Teresa

AU - Cockburn, Ian A.

PY - 2024/2/13

Y1 - 2024/2/13

N2 - 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 Ighg2A10 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.

AB - 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 Ighg2A10 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.

KW - B cells

KW - Plasmodium

KW - affinity maturation

KW - germinal center

KW - plasma cells

KW - single-cell RNA-seq

UR - http://www.scopus.com/inward/record.url?scp=85184748654&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2023.12.010

DO - 10.1016/j.immuni.2023.12.010

M3 - Article

SN - 1074-7613

VL - 57

SP - 245-255.e5

JO - Immunity

JF - Immunity

IS - 2

ER -

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

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