Fas Receptor Expression in Germinal-Center B Cells Is Essential for T and B Lymphocyte Homeostasis

Zhenyue Hao; Gordon S. Duncan; Jane Seagal; Yu Wen Su; Claire Hong; Jillian Haight; Nien Jung Chen; Andrew Elia; Andrew Wakeham; Wanda Y. Li; Jennifer Liepa; Geoffrey A. Wood; Stefano Casola; Klaus Rajewsky; Tak W. Mak

doi:10.1016/j.immuni.2008.07.016

Fas Receptor Expression in Germinal-Center B Cells Is Essential for T and B Lymphocyte Homeostasis

Zhenyue Hao^*, Gordon S. Duncan, Jane Seagal, Yu Wen Su, Claire Hong, Jillian Haight, Nien Jung Chen, Andrew Elia, Andrew Wakeham, Wanda Y. Li, Jennifer Liepa, Geoffrey A. Wood, Stefano Casola, Klaus Rajewsky, Tak W. Mak

^*Corresponding author for this work

Institute of Microbiology and Immunology

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

188 Scopus citations

Abstract

Fas is highly expressed in activated and germinal center (GC) B cells but can potentially be inactivated by misguided somatic hypermutation. We employed conditional Fas-deficient mice to investigate the physiological functions of Fas in various B cell subsets. B cell-specific Fas-deficient mice developed fatal lymphoproliferation due to activation of B cells and T cells. Ablation of Fas specifically in GC B cells reproduced the phenotype, indicating that the lymphoproliferation initiates in the GC environment. B cell-specific Fas-deficient mice also showed an accumulation of IgG1⁺ memory B cells expressing high amounts of CD80 and the expansion of CD28-expressing CD4⁺ Th cells. Blocking T cell-B cell interaction and GC formation completely prevented the fatal lymphoproliferation. Thus, Fas-mediated selection of GC B cells and the resulting memory B cell compartment is essential for maintaining the homeostasis of both T and B lymphocytes.

Original language	English
Pages (from-to)	615-627
Number of pages	13
Journal	Immunity
Volume	29
Issue number	4
DOIs	https://doi.org/10.1016/j.immuni.2008.07.016
State	Published - 17 Oct 2008

Keywords

CELLIMMUNO

UN SDGs

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

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10.1016/j.immuni.2008.07.016

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@article{013b4197804744718600e6ec1277f03b,

title = "Fas Receptor Expression in Germinal-Center B Cells Is Essential for T and B Lymphocyte Homeostasis",

abstract = "Fas is highly expressed in activated and germinal center (GC) B cells but can potentially be inactivated by misguided somatic hypermutation. We employed conditional Fas-deficient mice to investigate the physiological functions of Fas in various B cell subsets. B cell-specific Fas-deficient mice developed fatal lymphoproliferation due to activation of B cells and T cells. Ablation of Fas specifically in GC B cells reproduced the phenotype, indicating that the lymphoproliferation initiates in the GC environment. B cell-specific Fas-deficient mice also showed an accumulation of IgG1+ memory B cells expressing high amounts of CD80 and the expansion of CD28-expressing CD4+ Th cells. Blocking T cell-B cell interaction and GC formation completely prevented the fatal lymphoproliferation. Thus, Fas-mediated selection of GC B cells and the resulting memory B cell compartment is essential for maintaining the homeostasis of both T and B lymphocytes.",

keywords = "CELLIMMUNO",

author = "Zhenyue Hao and Duncan, {Gordon S.} and Jane Seagal and Su, {Yu Wen} and Claire Hong and Jillian Haight and Chen, {Nien Jung} and Andrew Elia and Andrew Wakeham and Li, {Wanda Y.} and Jennifer Liepa and Wood, {Geoffrey A.} and Stefano Casola and Klaus Rajewsky and Mak, {Tak W.}",

note = "Funding Information: We thank various Mak lab members for technical assistance, T. Calzascia for help with Th17 cell differentiation, Toronto Centre for Phenogenomics for help with histology, and M. Saunders for scientific editing. This work was supported by grants to T.W.M. from the Terry Fox Cancer Foundation, Canadian Institutes of Health Research, and Leukemia and Lymphoma Society; to Z.H. from Canadian Institutes of Health Research; and to K.R. from the Deutsche Forschungsgemeinschaft through SFB 243 and the National Institutes of Health (USA). ",

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doi = "10.1016/j.immuni.2008.07.016",

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pages = "615--627",

journal = "Immunity",

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T1 - Fas Receptor Expression in Germinal-Center B Cells Is Essential for T and B Lymphocyte Homeostasis

AU - Hao, Zhenyue

AU - Duncan, Gordon S.

AU - Seagal, Jane

AU - Su, Yu Wen

AU - Hong, Claire

AU - Haight, Jillian

AU - Chen, Nien Jung

AU - Elia, Andrew

AU - Wakeham, Andrew

AU - Li, Wanda Y.

AU - Liepa, Jennifer

AU - Wood, Geoffrey A.

AU - Casola, Stefano

AU - Rajewsky, Klaus

AU - Mak, Tak W.

N1 - Funding Information: We thank various Mak lab members for technical assistance, T. Calzascia for help with Th17 cell differentiation, Toronto Centre for Phenogenomics for help with histology, and M. Saunders for scientific editing. This work was supported by grants to T.W.M. from the Terry Fox Cancer Foundation, Canadian Institutes of Health Research, and Leukemia and Lymphoma Society; to Z.H. from Canadian Institutes of Health Research; and to K.R. from the Deutsche Forschungsgemeinschaft through SFB 243 and the National Institutes of Health (USA).

PY - 2008/10/17

Y1 - 2008/10/17

N2 - Fas is highly expressed in activated and germinal center (GC) B cells but can potentially be inactivated by misguided somatic hypermutation. We employed conditional Fas-deficient mice to investigate the physiological functions of Fas in various B cell subsets. B cell-specific Fas-deficient mice developed fatal lymphoproliferation due to activation of B cells and T cells. Ablation of Fas specifically in GC B cells reproduced the phenotype, indicating that the lymphoproliferation initiates in the GC environment. B cell-specific Fas-deficient mice also showed an accumulation of IgG1+ memory B cells expressing high amounts of CD80 and the expansion of CD28-expressing CD4+ Th cells. Blocking T cell-B cell interaction and GC formation completely prevented the fatal lymphoproliferation. Thus, Fas-mediated selection of GC B cells and the resulting memory B cell compartment is essential for maintaining the homeostasis of both T and B lymphocytes.

AB - Fas is highly expressed in activated and germinal center (GC) B cells but can potentially be inactivated by misguided somatic hypermutation. We employed conditional Fas-deficient mice to investigate the physiological functions of Fas in various B cell subsets. B cell-specific Fas-deficient mice developed fatal lymphoproliferation due to activation of B cells and T cells. Ablation of Fas specifically in GC B cells reproduced the phenotype, indicating that the lymphoproliferation initiates in the GC environment. B cell-specific Fas-deficient mice also showed an accumulation of IgG1+ memory B cells expressing high amounts of CD80 and the expansion of CD28-expressing CD4+ Th cells. Blocking T cell-B cell interaction and GC formation completely prevented the fatal lymphoproliferation. Thus, Fas-mediated selection of GC B cells and the resulting memory B cell compartment is essential for maintaining the homeostasis of both T and B lymphocytes.

KW - CELLIMMUNO

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AN - SCOPUS:53349167095

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VL - 29

SP - 615

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JO - Immunity

JF - Immunity

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ER -

Fas Receptor Expression in Germinal-Center B Cells Is Essential for T and B Lymphocyte Homeostasis

Abstract

Keywords

UN SDGs

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