ArticleMolecular immunology2008
Btk regulates localization, in vivo activation, and class switching of anti-DNA B cells.
Article in Molecular immunology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Selective Inhibition of Bruton's Tyrosine Kinase by a Designed Covalent Ligand Leads to Potent Therapeutic Efficacy in Blood Cancers Relative to Clinically Used Inhibitors.ACS pharmacology & translational science · 2022Article
- Human T-bet+ B cell development is associated with BTK activity and suppressed by evobrutinib.JCI insight · 2022Article
- B Cell Aberrance in Lupus: the Ringleader and the Solution.Clinical reviews in allergy & immunology · 2022Review
- Article
- Targeting Bruton's Tyrosine Kinase in Inflammatory and Autoimmune Pathologies.Frontiers in cell and developmental biology · 2021Review
- Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Toll-Like Receptor Signaling Drives Btk-Mediated Autoimmune Disease.Frontiers in immunology · 2019Article
- Bruton's Tyrosine Kinase Is Not Essential for B Cell Survival beyond Early Developmental Stages.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Intracellular B Lymphocyte Signalling and the Regulation of Humoral Immunity and Autoimmunity.Clinical reviews in allergy & immunology · 2017Review
- HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus.Arthritis research & therapy · 2017Article
- Reply.Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
- Bruton's Tyrosine Kinase, a Component of B Cell Signaling Pathways, Has Multiple Roles in the Pathogenesis of Lupus.Frontiers in immunology · 2017Review
- Bruton's Tyrosine Kinase Deficiency Inhibits Autoimmune Arthritis in Mice but Fails to Block Immune Complex-Mediated Inflammatory Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- The role of Bruton's tyrosine kinase in autoimmunity and implications for therapy.Expert review of clinical immunology · 2016Review
- Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation.Immunity, inflammation and disease · 2015Article
- Bruton's Tyrosine Kinase Synergizes with Notch2 To Govern Marginal Zone B Cells in Nonobese Diabetic Mice.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- The role of tyrosine kinases in systemic lupus erythematosus and their potential as therapeutic targets.Expert review of clinical immunology · 2014Review
- SLAP deficiency decreases dsDNA autoantibody production.Clinical immunology (Orlando, Fla.) · 2014Article
- The role of Bruton's tyrosine kinase in the development and BCR/TLR-dependent activation of AM14 rheumatoid factor B cells.Journal of leukocyte biology · 2013Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The autoimmune disease systemic lupus erythematosus (SLE) is characterized by loss of tolerance to nuclear antigens such as chromatin, DNA, and RNA. This focused autoreactivity is thought to arise from the ability of DNA or RNA specific B cells to receive dual signals from the BCR and TLR9 or TLR7, respectively. The Tec kinase Btk is necessary for the production of anti-DNA antibodies in several murine models of SLE. To assess the role of Btk in the fate of DNA reactive B cells, we generated Btk-/- mice carrying the 56R anti-DNA Ig transgene on the C57BL/6 background. dsDNA specific B cells were present in 56R.Btk-/- mice, although they were not preferentially localized to the marginal zone. These cells were able to proliferate in response to large CpG DNA containing fragments that require BCR-induced internalization to access TLR9. However, anti-DNA antibodies were not observed in the serum of 56R.Btk-/- mice. A transgene expressing a low level of Btk in B cells (Btk(lo)) restored anti-DNA IgM in these mice. This correlated with partial rescue of proliferative response to BCR engagement and TLR9-induced IL-10 secretion in Btk(lo) B cells. anti-DNA IgG was not observed in 56R.Btk(lo) mice, however. This was likely due, at least in part, to a role for Btk in controlling the expression of T-bet and AID in cells stimulated with CpG DNA. Thus, Btk is required for the initial loss of tolerance to DNA and the subsequent production of pathogenic autoantibodies once tolerance is breached.
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What OpenQuestion holds
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.