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Cited by 27T-cell and B-cell ImmunologyProtein Kinase Regulation and GTPase SignalingSignaling Pathways in Disease

Phospholipase Cγ2 Plays a Role in TCR Signal Transduction and T Cell Selection

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Fu, Guoping, Chen, Yuhong, Schuman, James, Wang, Demin, Wen, Renren·2012·The Journal of Immunology
DOI 10.4049/jimmunol.1103458PMC PMC3528184
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Abstract

One of the important signaling events following TCR engagement is activation of phospholipase Cγ (PLCγ). PLCγ has two isoforms, PLCγ1 and PLCγ2. It is known that PLCγ1 is important for TCR signaling and TCR-mediated T cell selection and functions, whereas PLCγ2 is critical for BCR signal transduction and BCR-mediated B cell maturation and functions. In this study, we report that PLCγ2 was expressed in primary T cells, and became associated with linker for activated T cells and Src homology 2-domain containing leukocyte protein of 76 kDa and activated upon TCR stimulation. PLCγ1/PLCγ2 double-deficient T cells displayed further block from CD4 and CD8 double-positive to single-positive transition compared with PLCγ1 single-deficient T cells. TCR-mediated proliferation was further impaired in PLCγ1/PLCγ2 double-deficient T cells compared with PLCγ1 single-deficient T cells. TCR-mediated signal transduction, including Ca2+ mobilization and Erk activation, was further impaired in PLCγ1/PLCγ2 double-deficient relative to PLCγ1 single-deficient T cells. In addition, in HY TCR transgenic mouse model, thymic positive and negative selections were reduced in PLCγ1 heterozygous- and PLCγ2 homozygous-deficient (PLCγ1+/−PLCγ2−/−) relative to wild-type, PLCγ2 single-deficient (PLCγ2−/−), or PLCγ1 heterozygous-deficient (PLCγ1+/−) mice. Taken together, these data demonstrate that PLCγ2 participates in TCR signal transduction and plays a role in T cell selection.

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  • PLCγ2 is primarily expressed in lymphoid tissue (bone marrow, thymus, spleen and lymph nodes), where it functions immediately downstream of the B-cell receptor (BCR) and other ITAM-coupled receptors.

    “PLCγ2 is primarily expressed in lymphoid tissue (bone marrow, thymus, spleen and lymph nodes), where it functions immediately downstream of the B-cell receptor (BCR) and other ITAM-coupled receptors [22–24].”

    From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [23]

    The Introduction says PLCγ2 expression is restricted to the hematopoietic system, and the Results identify it in thymic and splenic T cells; neither passage establishes primary expression across the four listed tissues. The Abstract says PLCγ2 is critical for BCR signal transduction, but our copy does not establish that it functions immediately downstream of the BCR and other ITAM-coupled receptors. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • PLCγ2 is required in primary T cells, in association with LAT and SLP-76, upon TCR stimulation; PLCγ1/2 double-mutant cells show impaired TCR signal transduction with regard to calcium flux and Erk activation compared with PLCγ1 KO alone.

    “However, PLCγ2 is required in primary T cells, in association with a linker for activated T cells and SH2 domain–containing leukocyte protein of 76 kDa (SLP-76), when signaling upon TCR stimulation, with PLCγ1/2 double-mutant cells showing impaired TCR signal transduction with regard to calcium flux and subsequent Erk activation compared with the PLCγ1 KO alone (61).”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [61]

    The Results sections report that PLCγ2 associates with LAT and SLP-76 after TCR stimulation and that double-deficient thymocytes have less calcium flux and Erk activation than PLCγ1-deficient thymocytes. But the Discussion says PLCγ2 deficiency alone appears not to affect TCR signaling, so calling it generally “required” in primary T cells overstates its role. Page numbers were not provided. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Authors
Fu, G., Chen, Y., Schuman, J., Wang, D., & Wen, R.
Affiliations
  • Versiti Blood Center of Wisconsin (US)
  • Medical College of Wisconsin (US)
Corresponding author
  • Fu, Guoping
  • Chen, Yuhong
  • Wang, Demin
  • Wen, Renren
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2012-09-01
Volume
189
Issue
5
Pages
2326-2332
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.1103458
PMC
PMC3528184
OpenAlex
W2096368044
Cited by
27
References
5
Citations by year
2026: 3 · 2025: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 6 · 2016: 1 · 2015: 1 · 2013: 1
FWCI
0.28
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (P01HL044612, P01-HL-44612)
  • National Institute of Allergy and Infectious Diseases (R56AI071239, R01AI079087, R01AI052327)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
PLCγ2, phospholipase C-gamma1, T cell receptor signaling, T cell selection, positive selection, negative selection, T cell development, calcium mobilization, ERK activation, T cell proliferation
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell, Thymus Gland, Signal Transduction, Mice, Knockout, Mice, Phospholipase C gamma, Primary Cell Culture

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