ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Bruton's tyrosine kinase promotes persistence of mature anti-insulin B cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The trial behind it
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single-Dose and Multiple-Rising-Dose Study of the BTK Inhibitor TAK-020 in Healthy Subjects.Clinical and translational science · 2021Trial
- The X Factor in Immunity: Sex Differences Shaped by the X Chromosome.Immunological reviews · 2026Review
- Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes.Antibodies (Basel, Switzerland) · 2024Review
- Autoimmunity in Primary Immunodeficiencies (PID).Clinical reviews in allergy & immunology · 2023Review
- COVID-19: Diabetes Perspective-Pathophysiology and Management.Pathogens (Basel, Switzerland) · 2023Review
- B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes.Biomedicines · 2021Review
- Targeting Bruton's Tyrosine Kinase in Inflammatory and Autoimmune Pathologies.Frontiers in cell and developmental biology · 2021Review
- COVID-19 and diabetes mellitus: from pathophysiology to clinical management.Nature reviews. Endocrinology · 2021Review
- Homeostasis and regulation of autoreactive B cells.Cellular & molecular immunology · 2020Review
- Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Anti-Insulin B Cells Are Poised for Antigen Presentation in Type 1 Diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Bruton's Tyrosine Kinase Is Not Essential for B Cell Survival beyond Early Developmental Stages.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Reply.Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
- 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
- Targeting Anti-Insulin B Cell Receptors Improves Receptor Editing in Type 1 Diabetes-Prone Mice.Journal of immunology (Baltimore, Md. : 1950) · 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
- Regulation of B lymphocytes and plasma cells by innate immune mechanisms and stromal cells in rheumatoid arthritis.Expert review of clinical immunology · 2014Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Autoreactive B lymphocytes are essential for the development of T cell-mediated type 1 diabetes (T1D). Cytoplasmic Bruton's tyrosine kinase (BTK) is a key component of B cell signaling, and its deletion in T1D-prone NOD mice significantly reduces diabetes. However, the role of BTK in the survival and function of autoreactive B cells is not clear. To evaluate the contributions of BTK, we used mice in which B cells express an anti-insulin BCR (125Tg) and promote T1D, despite being anergic. Crossing Btk deficiency onto 125Tg mice reveals that, in contrast to immature B cells, mature anti-insulin B cells are exquisitely dependent upon BTK, because their numbers are reduced by 95%. BTK kinase domain inhibition reproduces this effect in mature anti-insulin B cells, with less impact at transitional stages. The increased dependence of anti-insulin B cells on BTK became particularly evident in an Igκ locus site-directed model, in which 50% of B cells edit their BCRs to noninsulin specificities; Btk deficiency preferentially depletes insulin binders from the follicular and marginal zone B cell subsets. The persistent few Btk-deficient anti-insulin B cells remain competent to internalize Ag and invade pancreatic islets. As such, loss of BTK does not significantly reduce diabetes incidence in 125Tg/NOD mice as it does in NOD mice with a normal B cell repertoire. Thus, BTK targeting may not impair autoreactive anti-insulin B cell function, yet it may provide protection in an endogenous repertoire by decreasing the relative availability of mature autoreactive B cells.
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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.