Cutting Edge: Essential Role of Phospholipase C-γ2 in B Cell Development and Function
Open accessAbstract
Cross-linking of the B cell Ag receptor (BCR) induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-γ2, which is involved in the activation of the phosphatidylinositol pathway. To assess the importance of PLC-γ2 in murine lymphopoiesis, the PLC-γ2 gene was inducibly ablated by using IFN-regulated Cre recombinase. Mice with a neonatally induced loss of PLC-γ2 function displayed reduced numbers of mature conventional B cells and peritoneal B1 cells and defective responses in vitro to BCR stimulation and in vivo to immunization with thymus-independent type II Ags. In contrast, T cell development and TCR-mediated proliferation were normal. Taken together, PLC-γ2 is a critical component of BCR signaling pathways and is required to promote B cell development.
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PLCγ2 is highly expressed in hematopoietic cells and has a key role in signalling downstream of ITAM-associated receptors, controlling B cell and innate immune cell functions in response to BCR and FcR stimulation.
“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 [42]
The Discussion reports that PLCγ2 is a critical component of BCR signaling, and the Results show impaired B-cell responses to BCR stimulation when PLCγ2 is lost (page numbers unavailable in our copy). The cited paper does not establish the claim about high expression across hematopoietic cells, ITAM-associated receptors generally, or FcR-stimulated innate immune cell functions. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPLCγ2-deficient and inducible PLCγ2−/− mice lack the ability to respond to antigens.
“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 [26]
The Results report reduced IgM responses to both T-independent and T-dependent antigens in inducible PLCγ2-mutant mice. They do not support a complete inability to respond: T-dependent IgG responses were comparable to controls. This paper tests inducible mutants, not a separate group of constitutively PLCγ2-deficient mice. (LLM, conf=0.90)
Experimental — accuracy not yet measuredMicroglia activation of Plcg2 might regulate intracellular calcium release, as shown for B cells, and contribute to modulation of specific immune responses such as phagocytosis, migration, proliferation, and survival.
“In the brain, microglia activation of Plcg2 might regulate intracellular calcium release, as shown for B cells [12, 45], and contribute to the modulation of specific immune responses such as phagocytosis, migration, proliferation, and survival.”
From Alzheimer’s disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph (2019) · cites this paper as [45]
In the absence of PLCγ2, T cell development and TCR-mediated proliferation are normal, with development instead depending on PLCγ1.
“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 [26]
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- Authors
- Hashimoto, A., Takeda, K., Inaba, M., Sekimata, M., Kaisho, T., Ikehara, S., Homma, Y., Akira, S., & Kurosaki, T.
- Affiliations
- Kansai Medical University (JP)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Fukushima Medical University (JP)
- Corresponding author
- Hashimoto, Ari
- Kurosaki, Tomohiro
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-08
- Volume
- 165
- Issue
- 4
- Pages
- 1738-1742
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2153410622
- Cited by
- 155
- References
- 24
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 6
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- PLCγ2, B cell development, B cell receptor signaling, lymphocyte development, phosphatidylinositol pathway, tyrosine phosphorylation, thymus-independent antigens, Cre recombinase, T cell development
- MeSH terms
- Animals, Antigens, Surface, Antigens, T-Independent, B-Lymphocytes, Calcium, Cell Differentiation, Ficoll, Haptens, Hemocyanins, Immunoglobulin M, Isoenzymes, Lymphocyte Activation, Type C Phospholipases, T-Lymphocytes, Trinitrobenzenes, Lymphocyte Subsets, Gene Deletion, Mice, Knockout, Mice, Phospholipase C gamma
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