Cited by 22T-cell and B-cell ImmunologyLymphoma Diagnosis and TreatmentNF-κB Signaling Pathways

Phospholipase Cγ2 Contributes to Light-Chain Gene Activation and Receptor Editing

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Bai, Li, Chen, Yuhong, He, Yinghong, Dai, Xuezhi, Lin, Xueyan, Wen, Renren, Wang, Demin·2007·Molecular and Cellular Biology

Abstract

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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Crossref · 10.1128/mcb.02273-06

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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 measured
  • PLCγ2−/− 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 measured
  • PLCγ2 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).”

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Research works printed but not linked: 1

  1. [10]Engel, H., A. Rolink, and S. Weiss. 1999. B cells are programmed to activate kappa and lambda for rearrangement at consecutive developmental stages. Eur. J. Immunol. 29:2167-2176. [DOI] [PubMed] [Google Scholar]

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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
Published
2007-09
Volume
27
Issue
17
Pages
5957-5967
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
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
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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