Production of Ins(1,3,4,5)P4 mediated by the kinase Itpkb inhibits store-operated calcium channels and regulates B cell selection and activation.

Abstract:

:Antigen receptor-mediated production of inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) in lymphocytes triggers the release of Ca2+ from intracellular stores; this release of Ca2+ results in the opening of store-operated Ca2+ channels in the plasma membrane. Here we report that mice lacking Ins(1,4,5)P3 3-kinase B (Itpkb), which converts Ins(1,4,5)P3 to inositol-1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), had impaired B lymphocyte development and defective immunoglobulin G3 antibody responses to a T lymphocyte-independent antigen. Itpkb-deficient B lymphocytes had the phenotypic and functional features of tolerant B lymphocytes and showed enhanced activity of store-operated Ca2+ channels after B lymphocyte receptor stimulation, which was reversed by the provision of exogenous Ins(1,3,4,5)P4. Our data identify Itpkb and its product Ins(1,3,4,5)P4 as inhibitors of store-operated Ca2+ channels and crucial regulators of B cell selection and activation.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Miller AT,Sandberg M,Huang YH,Young M,Sutton S,Sauer K,Cooke MP

doi

10.1038/ni1458

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

514-21

issue

5

eissn

1529-2908

issn

1529-2916

pii

ni1458

journal_volume

8

pub_type

杂志文章
  • Dynamic regulation of hypoxia-inducible factor-1α activity is essential for normal B cell development.

    abstract::B lymphocyte development and selection are central to adaptive immunity and self-tolerance. These processes require B cell receptor (BCR) signaling and occur in bone marrow, an environment with variable hypoxia, but whether hypoxia-inducible factor (HIF) is involved is unknown. We show that HIF activity is high in hum...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0772-8

    authors: Burrows N,Bashford-Rogers RJM,Bhute VJ,Peñalver A,Ferdinand JR,Stewart BJ,Smith JEG,Deobagkar-Lele M,Giudice G,Connor TM,Inaba A,Bergamaschi L,Smith S,Tran MGB,Petsalaki E,Lyons PA,Espeli M,Huntly BJP,Smith KGC,Corn

    更新日期:2020-11-01 00:00:00

  • The impact of host genetic variation on infection with HIV-1.

    abstract::The outcome after infection with the human immunodeficiency virus type 1 (HIV-1) is a complex phenotype determined by interactions among the pathogen, the human host and the surrounding environment. An impact of host genetic variation on HIV-1 susceptibility was identified early in the pandemic, with a major role attr...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.3147

    authors: McLaren PJ,Carrington M

    更新日期:2015-06-01 00:00:00

  • Nonspecific effects of neonatal and infant vaccination: public-health, immunological and conceptual challenges.

    abstract::Vaccines can have nonspecific effects through their modulation of responses to infections not specifically targeted by the vaccine. However, lack of knowledge about the underlying immunological mechanisms and molecular cause-and-effect relationships prevent use of this potentially powerful early-life intervention to i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2961

    authors: Aaby P,Kollmann TR,Benn CS

    更新日期:2014-10-01 00:00:00

  • Stem cell-immune cell cross-talk.

    abstract:: ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-018-0282-0

    authors: Visan I

    更新日期:2019-01-01 00:00:00

  • STEEP mediates STING ER exit and activation of signaling.

    abstract::STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signal...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0730-5

    authors: Zhang BC,Nandakumar R,Reinert LS,Huang J,Laustsen A,Gao ZL,Sun CL,Jensen SB,Troldborg A,Assil S,Berthelsen MF,Scavenius C,Zhang Y,Windross SJ,Olagnier D,Prabakaran T,Bodda C,Narita R,Cai Y,Zhang CG,Stenmark H,Do

    更新日期:2020-08-01 00:00:00

  • Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection.

    abstract::Progenitor-like CD8+ T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct pr...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0403-4

    authors: Yao C,Sun HW,Lacey NE,Ji Y,Moseman EA,Shih HY,Heuston EF,Kirby M,Anderson S,Cheng J,Khan O,Handon R,Reilley J,Fioravanti J,Hu J,Gossa S,Wherry EJ,Gattinoni L,McGavern DB,O'Shea JJ,Schwartzberg PL,Wu T

    更新日期:2019-07-01 00:00:00

  • Intrinsic immunity: a front-line defense against viral attack.

    abstract::In addition to the conventional innate and acquired immune responses, complex organisms have evolved an array of dominant, constitutively expressed genes that suppress or prevent viral infections. Two major cellular defenses against infection by retroviruses are the Fv1 and TRIM5 class of inhibitors that target incomi...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni1125

    authors: Bieniasz PD

    更新日期:2004-11-01 00:00:00

  • The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells.

    abstract::Intestinal microfold cells (M cells) are an enigmatic lineage of intestinal epithelial cells that initiate mucosal immune responses through the uptake and transcytosis of luminal antigens. The mechanisms of M-cell differentiation are poorly understood, as the rarity of these cells has hampered analysis. Exogenous admi...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2352

    authors: Kanaya T,Hase K,Takahashi D,Fukuda S,Hoshino K,Sasaki I,Hemmi H,Knoop KA,Kumar N,Sato M,Katsuno T,Yokosuka O,Toyooka K,Nakai K,Sakamoto A,Kitahara Y,Jinnohara T,McSorley SJ,Kaisho T,Williams IR,Ohno H

    更新日期:2012-06-17 00:00:00

  • Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation.

    abstract::Although tissue-resident memory T cells (TRM cells) have been shown to regulate host protection in infectious disorders, their function in inflammatory bowel disease (IBD) remains to be investigated. Here we characterized TRM cells in human IBD and in experimental models of intestinal inflammation. Pro-inflammatory TR...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-018-0298-5

    authors: Zundler S,Becker E,Spocinska M,Slawik M,Parga-Vidal L,Stark R,Wiendl M,Atreya R,Rath T,Leppkes M,Hildner K,López-Posadas R,Lukassen S,Ekici AB,Neufert C,Atreya I,van Gisbergen KPJM,Neurath MF

    更新日期:2019-03-01 00:00:00

  • Deletion of a coordinate regulator of type 2 cytokine expression in mice.

    abstract::Mechanisms that underlie the patterning of cytokine expression in T helper (T(H)) cell subsets remain incompletely defined. An evolutionarily conserved approximately 400-bp noncoding sequence in the intergenic region between the genes Il4 and Il13, designated conserved noncoding sequence 1 (CNS-1), was deleted in mice...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni0901-842

    authors: Mohrs M,Blankespoor CM,Wang ZE,Loots GG,Afzal V,Hadeiba H,Shinkai K,Rubin EM,Locksley RM

    更新日期:2001-09-01 00:00:00

  • T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2.

    abstract::The lineage commitment of CD4+ T cells is coordinately regulated by signals through the T cell receptor and cytokine receptors, yet how these signals are integrated remains elusive. Here we find that mice lacking Dock2, a Rac activator in lymphocytes, developed allergic disease through a mechanism dependent on CD4+ T ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1506

    authors: Tanaka Y,Hamano S,Gotoh K,Murata Y,Kunisaki Y,Nishikimi A,Takii R,Kawaguchi M,Inayoshi A,Masuko S,Himeno K,Sasazuki T,Fukui Y

    更新日期:2007-10-01 00:00:00

  • CCR5 provides a signal for microbial induced production of IL-12 by CD8 alpha+ dendritic cells.

    abstract::The activation of dendritic cells (DC) to produce interleukin 12 (IL-12) is thought to be a key step in the initiation of cell-mediated immunity to intracellular pathogens. Here we show that ligation of the C-C chemokine receptor (CCR) 5 can provide a major signal for the induction of IL-12 synthesis by the CD8 alpha+...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/76957

    authors: Aliberti J,Reis e Sousa C,Schito M,Hieny S,Wells T,Huffnagle GB,Sher A

    更新日期:2000-07-01 00:00:00

  • Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12.

    abstract::Innate lymphoid cells (ILCs) are tissue-resident sentinels that are essential for early host protection from pathogens at initial sites of infection. However, whether pathogen-derived antigens directly modulate the responses of tissue-resident ILCs has remained unclear. In the present study, it was found that liver-re...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0430-1

    authors: Weizman OE,Song E,Adams NM,Hildreth AD,Riggan L,Krishna C,Aguilar OA,Leslie CS,Carlyle JR,Sun JC,O'Sullivan TE

    更新日期:2019-08-01 00:00:00

  • The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling.

    abstract::The mechanisms that initiate T helper type 2 (T(H)2) responses are poorly understood. Here we demonstrate that cysteine protease-induced T(H)2 responses occur via 'cooperation' between migratory dermal dendritic cells (DCs) and basophils positive for interleukin 4 (IL-4). Subcutaneous immunization with papain plus ant...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1883

    authors: Tang H,Cao W,Kasturi SP,Ravindran R,Nakaya HI,Kundu K,Murthy N,Kepler TB,Malissen B,Pulendran B

    更新日期:2010-07-01 00:00:00

  • Publisher Correction: Macrophages: damage control.

    abstract::In the version of this Research Highlight initially published, the url for the linked article was incorrect ( https://doi.org/10.1172/JCI90647JCI90647 ). The correct link is https://doi.org/10.1172/JCI90647 . The error has been corrected in the HTML and PDF versions of the article. ...

    journal_title:Nature immunology

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41590-018-0159-2

    authors: Fehervari Z

    更新日期:2018-08-01 00:00:00

  • Regulating T helper cell immunity through antigen responsiveness and calcium entry.

    abstract::We evaluated changes in the signaling potentials and proliferative capacity of single antigen-specific T helper (TH) cells during a primary immune response to a protein antigen. At the peak of cellular expansion in vivo all antigen-specific TH cells exhibited a profound block in CD3- and CD4-mediated mobilization of i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/80841

    authors: Bikah G,Pogue-Caley RR,McHeyzer-Williams LJ,McHeyzer-Williams MG

    更新日期:2000-11-01 00:00:00

  • RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation.

    abstract::Stimulation of Toll-like receptors (TLRs) initiates potent innate immune responses through Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88 and Trif. Analysis of Trif-deficient mice has shown that TLR3-dependent activation of the transcription factor NF-kappa B by the TLR3 ligand double-stran...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1061

    authors: Meylan E,Burns K,Hofmann K,Blancheteau V,Martinon F,Kelliher M,Tschopp J

    更新日期:2004-05-01 00:00:00

  • Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells.

    abstract::Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4(+) T cells undergo less-efficient homeostatic proliferation than CD8(+) T cells do. Here we show that systemic IL-7 concentrations increased during ly...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1695

    authors: Guimond M,Veenstra RG,Grindler DJ,Zhang H,Cui Y,Murphy RD,Kim SY,Na R,Hennighausen L,Kurtulus S,Erman B,Matzinger P,Merchant MS,Mackall CL

    更新日期:2009-02-01 00:00:00

  • Single-cell technologies for monitoring immune systems.

    abstract::The complex heterogeneity of cells, and their interconnectedness with each other, are major challenges to identifying clinically relevant measurements that reflect the state and capability of the immune system. Highly multiplexed, single-cell technologies may be critical for identifying correlates of disease or immuno...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2796

    authors: Chattopadhyay PK,Gierahn TM,Roederer M,Love JC

    更新日期:2014-02-01 00:00:00

  • Fiber against flu.

    abstract:: ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-018-0147-6

    authors: Visan I

    更新日期:2018-07-01 00:00:00

  • Dynamic expression of transcription factors T-bet and GATA-3 by regulatory T cells maintains immunotolerance.

    abstract::Regulatory T cells (Treg cells) can express the transcription factors T-bet and GATA-3, but the function of this expression and whether such cells represent stable subsets is still unknown. By using various reporter tools, we found that the expression of T-bet and GATA-3 in Treg cells was dynamically influenced by the...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3053

    authors: Yu F,Sharma S,Edwards J,Feigenbaum L,Zhu J

    更新日期:2015-02-01 00:00:00

  • Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5.

    abstract::Rearrangement of immunoglobulin heavy-chain variable (V(H)) gene segments has been suggested to be regulated by interleukin 7 signaling in pro-B cells. However, the genetic evidence for this recombination pathway has been challenged. Furthermore, no molecular components that directly control V(H) gene rearrangement ha...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1226

    authors: Bertolino E,Reddy K,Medina KL,Parganas E,Ihle J,Singh H

    更新日期:2005-08-01 00:00:00

  • The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses.

    abstract::Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T helper type 2 (TH2), but not TH1, allergic responses in both the skin and lungs. Loss of STAT5 ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2541

    authors: Bell BD,Kitajima M,Larson RP,Stoklasek TA,Dang K,Sakamoto K,Wagner KU,Kaplan DH,Reizis B,Hennighausen L,Ziegler SF

    更新日期:2013-04-01 00:00:00

  • Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.

    abstract::Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8α(+) (CD103(+)) cDC1 lineage, and the CD11b(+) cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3200

    authors: Schlitzer A,Sivakamasundari V,Chen J,Sumatoh HR,Schreuder J,Lum J,Malleret B,Zhang S,Larbi A,Zolezzi F,Renia L,Poidinger M,Naik S,Newell EW,Robson P,Ginhoux F

    更新日期:2015-07-01 00:00:00

  • The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3.

    abstract::Viral infection induces type I interferons (IFN-alpha and IFN-beta) that recruit unexposed cells in a self-amplifying response. We report that the transcription factor MafB thwarts auto-amplification by a metastable switch activity. MafB acted as a weak positive basal regulator of transcription at the IFNB1 promoter t...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1897

    authors: Kim H,Seed B

    更新日期:2010-08-01 00:00:00

  • Renaissance for mouse models of human hematopoiesis and immunobiology.

    abstract::More than 20 years after the first successful engraftment of human leukocytes and hematopoietic organs in mice, scientists met for the 2nd International Workshop on Humanized Mice to discuss progress and to highlight expectations in this dynamic field. ...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni1009-1039

    authors: Manz MG,Di Santo JP

    更新日期:2009-10-01 00:00:00

  • A comprehensive analysis of the effects of the deaminase AID on the transcriptome and methylome of activated B cells.

    abstract::Beyond its well-characterized functions in antibody diversification, the cytidine deaminase AID can catalyze off-target DNA damage and has been hypothesized to edit RNA and mediate DNA demethylation. To comprehensively examine the effects of AID on the transcriptome and the pattern of DNA methylation ('methylome'), we...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2616

    authors: Fritz EL,Rosenberg BR,Lay K,Mihailović A,Tuschl T,Papavasiliou FN

    更新日期:2013-07-01 00:00:00

  • Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity.

    abstract::Caspases are important for apoptosis but are also involved in mammalian cell survival and cell division. Here we report that caspase-3 is a negative regulator of B cell cycling. Mice deficient in caspase-3 (Casp3-/- mice) have increased numbers of splenic B cells that show normal apoptosis but enhanced proliferation i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni976

    authors: Woo M,Hakem R,Furlonger C,Hakem A,Duncan GS,Sasaki T,Bouchard D,Lu L,Wu GE,Paige CJ,Mak TW

    更新日期:2003-10-01 00:00:00

  • Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse.

    abstract::Actin reorganization at the immunological synapse is required for the amplification and generation of a functional immune response. Using small interfering RNA, we show here that dynamin 2 (Dyn2), a large GTPase involved in receptor-mediated internalization, did not alter antibody-mediated T cell receptor internalizat...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1168

    authors: Gomez TS,Hamann MJ,McCarney S,Savoy DN,Lubking CM,Heldebrant MP,Labno CM,McKean DJ,McNiven MA,Burkhardt JK,Billadeau DD

    更新日期:2005-03-01 00:00:00

  • B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities.

    abstract::The present paradigm dictates that phagocytosis is accomplished mainly by 'professional' phagocytes (such as macrophages and monocytes), whereas B cells lack phagocytic capabilities. Here we demonstrate that B cells from teleost fish have potent in vitro and in vivo phagocytic activities. Particle uptake by B cells in...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1389

    authors: Li J,Barreda DR,Zhang YA,Boshra H,Gelman AE,Lapatra S,Tort L,Sunyer JO

    更新日期:2006-10-01 00:00:00