The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index.
Phospholipase Cγ2 Is Essential in the Functions of B Cell and Several Fc Receptors
Open accessAbstract
Many receptors activate phospholipase Cgamma1 or -gamma2. To assess the role of PLCgamma2, we derived enzyme-deficient mice. The mice are viable but have decreased mature B cells, a block in pro-B cell differentiation, and B1 B cell deficiency. IgM receptor-induced Ca2+ flux and proliferation to B cell mitogens are absent. IgM, IgG2a, and IgG3 levels are reduced, and T cell-independent antibody production is absent. The similarity to Btk- or Blnk-deficient mice demonstrates that PLCgamma2 is downstream in Btk/Blnk signaling. FcRgamma signaling is also defective, resulting in a loss of collagen-induced platelet aggregation, mast cell FcepsilonR function, and NK cell FcgammaRIII and 2B4 function. The results define a signal transduction pathway broadly utilized by immunoglobulin superfamily receptors.
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In the citing paper
“In fact, a previous study reported marked decreases in the most mature B cell population in Plcg2 deficient mice(30).”
From Multi-omics analyses reveal novel effects of PLCγ2 deficiency in the mouse brain (2023) · cites this paper as [30]
In the citing paper
“Previous studies have reported internal hemorrhaging during development in other Plcg2 deficient mouse models (29, 30), which have been proposed to be caused by rupture of blood-filled fragile lymphatic vessels by mechanical stress or pressure of the blood flow (29).”
From Multi-omics analyses reveal novel effects of PLCγ2 deficiency in the mouse brain (2023) · cites this paper as [30]
In the citing paper
“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 [22]
In the citing paper
“In peripheral immune cells, PLCγ2 has been implicated in signaling pathways downstream of the B cell receptor, and it is thought to modulate the functions of macrophages, platelets, mast cells, neutrophils, and NK cells through the Fc receptor [14].”
From Alzheimer’s disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph (2019) · cites this paper as [14]
In the citing paper
“In different models of PLCG2 depletion, homozygous knockout embryos were found to have significant subcutaneous hemorrhaging, suggesting impacted vascular development and bleeding that may underlie embryonic death and reduced frequencies at weaning.”
From PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology (2025) · cites this paper as [19]
In the citing paper
“PLCγ2, highly expressed in hematopoietic cells, has the key role in signalling downstream of ITAM-associated receptors; for example, it controls multiple functions of B cells, and several types of innate immune cells in response to stimulation of the B-cell antigen receptor (BCR) and Fc receptors (FcRs), respectively [41,42].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [41]
In the citing paper
“Unlike the germline deletion of PLCγ2 that results in embryonic lethality, mice lacking PLCγ2 enzymatic activity were viable, but with profound defects in B cell development and function. These mice exhibited reduced mature B cells, disrupted differentiation of pro-B cells, and a lack of B1 B cells (24).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [24]
In the citing paper
“Indeed, PLCγ2-deficient and inducible PLCγ2−/− mice have been widely shown to lack the ability to respond to antigens (24, 26, 27, 28).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [24]
In the citing paper
“Inducible KO mice showed T cell development and T cell receptor (TCR)-mediated proliferation were normal in the absence of PLCγ2 (24, 26), with development instead depending on the closely related family member PLCγ1 (60).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [24]
In the citing paper
“On the other hand, PLCγ2 is more broadly present in myeloid cells [5, 25, 26], neutrophils [25, 27], mast cells [25], NK cells [5, 25], B-cells and platelets [5, 28, 29]”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [5]
In the citing paper
“These proteins are critical for the proper maturation, maintenance and function of a range of immune and hematopoietic-lineage cells [5, 23].”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [5]
In the citing paper
“PLCγ2 is expressed in cells of the hematopoietic lineage [5].”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [5]
In the citing paper
“In these cells, PLCγ2, downstream of B-cell receptor and Fc receptor signalling, regulates calcium-dependent functions supporting immune and inflammatory responses [5, 28].”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [5]
In the citing paper
“the deficits in B-cell development and function are the more pronounced effects described to date”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [5]
In the citing paper
“PLCγ2-deficient mice are viable, but exhibit haemorrhaging in various organs in addition to severe immunodeficiency [5]”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [5]
In the citing paper
“These include completely ablated calcium responses downstream of the B-cell receptor, affecting the ability to respond to stimuli, and reduced antibody production [5]”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [5]
In the citing paper
“In both humans and mice, PLCγ2 loss, as well as strong GOF, mostly results in detrimental and sometimes overlapping phenotypes, as largely described for the peripheral immune system [5, 25]”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [5]
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Metadata
- Authors
- Wang, D., Feng, J., Wen, R., Marine, J.-C., Sangster, M. Y., Parganas, E., Hoffmeyer, A., Jackson, C. W., Cleveland, J. L., Murray, P. J., & Ihle, J. N.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Ihle, James N.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 13
- Issue
- 1
- Pages
- 25-35
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2039490597
- Cited by
- 475
- References
- 54
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 5 · 2023: 12 · 2022: 4 · 2021: 13 · 2020: 11 · 2019: 10 · 2018: 6 · 2017: 10 · 2016: 12 · 2015: 16 · 2014: 12 · 2013: 14 · 2012: 16
- FWCI
- 12.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL053749, P01HL53749)
- National Cancer Institute (CA21765, P30CA021765)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK42932, R01DK042932)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- PLCγ2, B cell development, calcium flux, BTK signaling, 2B4, immunoglobulin superfamily receptors, platelet aggregation
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Animals, B-Lymphocytes, Blood Platelets, Carrier Proteins, Hematopoiesis, Isoenzymes, Mice, Inbred C57BL, Type C Phospholipases, Phosphoproteins, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Receptors, IgG, Mice, Knockout, Adaptor Proteins, Signal Transducing, Mice, Phospholipase C gamma
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