ArticleThe Journal of experimental medicine2010
Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
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- IQGAP1 promotes early B cell development, is essential for the development of marginal zone (MZ) B cells, and is critical for both T-dependent and T-independent antibody responses.Cellular and molecular life sciences : CMLS · 2024Article
- Diacylglycerol kinase is a keystone regulator of signaling relevant to the pathophysiology of asthma.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- Regulation of Foxo1 expression is critical for central B cell tolerance and allelic exclusion.Cell reports · 2024Article
- Exploiting Tertiary Lymphoid Structures to Stimulate Antitumor Immunity and Improve Immunotherapy Efficacy.Cancer research · 2024Article
- Design and deep learning of synthetic B-cell-specific promoters.Nucleic acids research · 2023Article
- Article
- Integrin β1 regulates marginal zone B cell differentiation and PI3K signaling.The Journal of experimental medicine · 2023Article
- CD19 Is Internalized Together with IgM in Proportion to B Cell Receptor Stimulation and Is Modulated by Phosphatidylinositol 3-Kinase in Bone Marrow Immature B Cells.ImmunoHorizons · 2023Article
- Regulation of the immune system by the insulin receptor in health and disease.Frontiers in endocrinology · 2023Review
- B-cell intrinsic and extrinsic signals that regulate central tolerance of mouse and human B cells.Immunological reviews · 2022Review
- FCRL1 Regulates B Cell Receptor-Induced ERK Activation through GRB2.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- MicroRNA regulation of B cell receptor signaling.Immunological reviews · 2021Review
- Bruton's tyrosine kinase inhibition induces rewiring of proximal and distal B-cell receptor signaling in mice.European journal of immunology · 2021Article
- A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases.Journal of clinical immunology · 2020Article
- Active PI3K abrogates central tolerance in high-avidity autoreactive B cells.The Journal of experimental medicine · 2019Article
- Strategies to Address Chimeric Antigen Receptor Tonic Signaling.Molecular cancer therapeutics · 2018Review
- Grb2 and GRAP connect the B cell antigen receptor to Erk MAP kinase activation in human B cells.Scientific reports · 2018Article
- Autoimmunity checkpoints as therapeutic targets in B cell malignancies.Nature reviews. Cancer · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
B cell receptors (BCRs) generate tonic signals critical for B cell survival and early B cell development. To determine whether these signals also mediate the development of transitional and mature B cells, we examined B cell development using a mouse strain in which nonautoreactive immunoglobulin heavy and light chain-targeted B cells express low surface BCR levels. We found that reduced BCR expression translated into diminished tonic BCR signals that strongly impaired the development of transitional and mature B cells. Constitutive expression of Bcl-2 did not rescue the differentiation of BCR-low B cells, suggesting that this defect was not related to decreased cell survival. In contrast, activation of the Ras pathway rescued the differentiation of BCR-low immature B cells both in vitro and in vivo, whereas extracellular signal-regulated kinase (Erk) inhibition impaired the differentiation of normal immature B cells. These results strongly suggest that tonic BCR signaling mediates the differentiation of immature into transitional and mature B cells via activation of Erk, likely through a pathway requiring Ras.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.