Phospholipase Cγ2 Contributes to Light-Chain Gene Activation and Receptor Editing
Open accessAbstract
Phospholipase Cgamma2 (PLCgamma2) is critical for pre-B-cell receptor (pre-BCR) and BCR signaling. Current studies discovered that PLCgamma2-deficient mice had reduced immunoglobulin lambda (Iglambda) light-chain usage throughout B-cell maturation stages, including transitional type 1 (T1), transitional type 2 (T2), and mature follicular B cells. The reduction of Iglambda rearrangement by PLCgamma2 deficiency was not due to specifically increased apoptosis or decreased proliferation of mutant Iglambda+ B cells, as lack of PLCgamma2 exerted a similar effect on apoptosis and proliferation of both Iglambda+ and Igkappa+ B cells. Moreover, PLCgamma2-deficient IgHEL transgenic B cells exhibited an impairment of antigen-induced receptor editing among both the endogenous lambda and kappa loci in vitro and in vivo. Importantly, PLCgamma2 deficiency impaired BCR-induced expression of IRF-4 and IRF-8, the two transcription factors critical for lambda and kappa light-chain rearrangements. Taken together, these data demonstrate that the PLCgamma2 signaling pathway plays a role in activation of light-chain loci and contributes to receptor editing.
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PLCγ2-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 [28]
The Discussion (page unavailable) reports impaired antigen-induced receptor editing in PLCγ2-deficient mice, and the Results (page unavailable) report severely impaired antigen-induced IRF-4 and IRF-8 expression. These are specific impaired responses, not evidence that the mice cannot respond to antigens at all. Our copy also does not establish the claim for inducible PLCγ2−/− mice. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPLCγ2−/− mice show a block in B cell maturation from transitional 2 to follicular B cells, with increased BCR-induced apoptosis.
“The first PLCγ2−/− mouse studies showed a block in B cell maturation from transitional 2 to follicular B cells, with these cells also exhibiting increased levels of BCR-induced apoptosis (28, 32).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [28]
The Discussion (page not provided) says PLCγ2 is essential for maturation from T2 to follicular B cells, citing previous studies. It does not report increased BCR-induced apoptosis in those cells; the Results (page not provided) instead examine apoptosis in freshly isolated cells, which does not test that claim. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPLCγ2 is important for light-chain loci activation, required for recombination and receptor editing of autoreactive B cells.
“The importance of PLCγ2 was additionally shown in terms of light-chain loci activation, required for recombination and receptor editing of autoreactive B cells (28).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [28]
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Khan, S. N., Cox, J. V., Nishimoto, S. K., Chen, C., Fritzler, M. J., Hendershot, L. M., WEIGERT, M. G., & Radic, M. Z. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1101336 · Cited by 6 · see citing works
Kidins220 regulates the development of B cells bearing the λ light chain
Schaffer, A.-M., Fiala, G. J., Hils, M., Natali, E. N., Babrak, L. M., Herr, L. A., Romero-Mulero, M. C., Cabezas‐Wallscheid, N., Rizzi, M., Miho, E., et al. (2023) · eLife · doi:10.7554/elife.83943 · Cited by 1 · see citing works
Autoinflammatory Diseases Affecting Predominantly the Skin
Milner, J. D. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405546-9.00027-3
Gfi1b Negatively Regulates the V(D)J Recombinase
Schulz, E. D. (2010) · eScholarship (California Digital Library)
- Authors
- Bai, L., Chen, Y., He, Y., Dai, X., Lin, X., Wen, R., & Wang, D.
- Affiliations
- Sun Yat-sen University (CN)
- Versiti Blood Center of Wisconsin (US)
- Medical College of Wisconsin (US)
- Corresponding author
- Wang, Demin
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-09
- Volume
- 27
- Issue
- 17
- Pages
- 5957-5967
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1952164
- OpenAlex
- W2033272706
- Cited by
- 22
- References
- 74
- Citations by year
- 2023: 2 · 2021: 1 · 2019: 1 · 2017: 3 · 2015: 4 · 2014: 2 · 2013: 1
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL073284)
- National Institute of Allergy and Infectious Diseases (R01AI052327, R01 AI52327)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- PLCγ2, lambda light chain, immunoglobulin kappa light chain, receptor editing, B cell receptor signaling, pre-B cell receptor signaling, transitional B cells, follicular B cells, IRF4, IRF8, B cell maturation
- MeSH terms
- Interferon Regulatory Factor-8, Interferon Regulatory Factor-4, Animals, B-Lymphocytes, Gene Expression Regulation, Immunoglobulin Light Chains, Mice, Inbred C57BL, Mice, Transgenic, Gene Rearrangement, B-Lymphocyte, Signal Transduction, Transcriptional Activation, Apoptosis, Mice, Knockout, Cell Proliferation, Interferon Regulatory Factors, Mice, Phospholipase C gamma, Pre-B Cell Receptors
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