Proapoptotic BIM Impacts B Lymphoid Homeostasis by Limiting the Survival of Mature B Cells in a Cell-Autonomous Manner.

Abstract:

:The proapoptotic BH3-only protein BIM (Bcl2l11) plays key roles in the maintenance of multiple hematopoietic cell types. In mice, germline knockout or conditional pan-hematopoietic deletion of Bim results in marked splenomegaly and significantly increased numbers of B cells. However, it has remained unclear whether these abnormalities reflect the loss of cell-intrinsic functions of BIM within the B lymphoid lineage and, if so, which stages in the lifecycle of B cells are most impacted by the loss of BIM. Here, we show that B lymphoid-specific conditional deletion of Bim during early development (i.e., in pro-B cells using Mb1-Cre) or during the final differentiation steps (i.e., in transitional B cells using Cd23-Cre) led to a similar >2-fold expansion of the mature follicular B cell pool. Notably, while the expansion of mature B cells was quantitatively similar in conditional and germline Bim-deficient mice, the splenomegaly was significantly attenuated after B lymphoid-specific compared to global Bim deletion. In vitro, conditional loss of Bim substantially increased the survival of mature B cells that were refractory to activation by lipopolysaccharide. Finally, we also found that conditional deletion of just one Bim allele by Mb1-Cre dramatically accelerated the development of Myc-driven B cell lymphoma, in a manner that was comparable to the effect of germline Bim heterozygosity. These data indicate that, under physiological conditions, BIM regulates B cell homeostasis predominantly by limiting the life span of non-activated mature B cells, and that it can have additional effects on developing B cells under pathological conditions.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Liu R,King A,Bouillet P,Tarlinton DM,Strasser A,Heierhorst J

doi

10.3389/fimmu.2018.00592

subject

Has Abstract

pub_date

2018-03-22 00:00:00

pages

592

issn

1664-3224

journal_volume

9

pub_type

杂志文章
  • Vaccines for canine leishmaniasis.

    abstract::Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with imm...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00069

    authors: Palatnik-de-Sousa CB

    更新日期:2012-04-17 00:00:00

  • The Interaction Mechanism Between Herpes Simplex Virus 1 Glycoprotein D and Host Antiviral Protein Viperin.

    abstract::Viperin is an interferon-inducible protein that responsible for a variety of antiviral responses to different viruses. Our previous study has shown that the ribonuclease UL41 of herpes simplex virus 1 (HSV-1) can degrade the mRNA of viperin to promote HSV-1 replication. However, it is not clear whether other HSV-1 enc...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02810

    authors: Li M,Liao Z,Xu Z,Zou X,Wang Y,Peng H,Li Y,Ou X,Deng Y,Guo Y,Gan W,Peng T,Chen D,Cai M

    更新日期:2019-12-11 00:00:00

  • TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter.

    abstract::TonEBP is a key transcriptional activator in macrophages with an M1 phenotype. High expression of TonEBP is associated with many inflammatory diseases. Heme oxygenase-1 (HO-1), a stress-inducible protein, is induced by various oxidative and inflammatory signals, and its expression is regarded as an adaptive cellular r...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00850

    authors: Yoo EJ,Lee HH,Ye BJ,Lee JH,Lee CY,Kang HJ,Jeong GW,Park H,Lim SW,Lee-Kwon W,Kwon HM,Choi SY

    更新日期:2019-04-18 00:00:00

  • IMPre: An Accurate and Efficient Software for Prediction of T- and B-Cell Receptor Germline Genes and Alleles from Rearranged Repertoire Data.

    abstract::Large-scale study of the properties of T-cell receptor (TCR) and B-cell receptor (BCR) repertoires through next-generation sequencing is providing excellent insights into the understanding of adaptive immune responses. Variable(Diversity)Joining [V(D)J] germline genes and alleles must be characterized in detail to fac...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2016.00457

    authors: Zhang W,Wang IM,Wang C,Lin L,Chai X,Wu J,Bett AJ,Dhanasekaran G,Casimiro DR,Liu X

    更新日期:2016-11-04 00:00:00

  • Directed Differentiation of Human Induced Pluripotent Stem Cells into Dendritic Cells Displaying Tolerogenic Properties and Resembling the CD141+ Subset.

    abstract::The advent of induced pluripotent stem cells (iPSCs) has begun to revolutionize cell therapy by providing a convenient source of rare cell types not normally available from patients in sufficient numbers for therapeutic purposes. In particular, the development of protocols for the differentiation of populations of leu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01935

    authors: Sachamitr P,Leishman AJ,Davies TJ,Fairchild PJ

    更新日期:2018-01-08 00:00:00

  • IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction.

    abstract::Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,随机对照试验

    doi:10.3389/fimmu.2018.02035

    authors: Orrem HL,Nilsson PH,Pischke SE,Kleveland O,Yndestad A,Ekholt K,Damås JK,Espevik T,Bendz B,Halvorsen B,Gregersen I,Wiseth R,Andersen GØ,Ueland T,Gullestad L,Aukrust P,Barratt-Due A,Mollnes TE

    更新日期:2018-09-12 00:00:00

  • Vitamin D in Acute Campylobacteriosis-Results From an Intervention Study Applying a Clinical Campylobacter jejuni Induced Enterocolitis Model.

    abstract::Human Campylobacter infections are progressively rising and of high socioeconomic impact. In the present preclinical intervention study we investigated anti-pathogenic, immuno-modulatory, and intestinal epithelial barrier preserving properties of vitamin D applying an acute campylobacteriosis model. Therefore, seconda...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02094

    authors: Mousavi S,Lobo de Sá FD,Schulzke JD,Bücker R,Bereswill S,Heimesaat MM

    更新日期:2019-09-03 00:00:00

  • A Comparison of the Innate and Adaptive Immune Systems in Cartilaginous Fish, Ray-Finned Fish, and Lobe-Finned Fish.

    abstract::The immune system is composed of two subsystems-the innate immune system and the adaptive immune system. The innate immune system is the first to respond to pathogens and does not retain memory of previous responses. Innate immune responses are evolutionarily older than adaptive responses and elements of innate immuni...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02292

    authors: Smith NC,Rise ML,Christian SL

    更新日期:2019-10-10 00:00:00

  • The Role of Mucosal Immunity in Pertussis.

    abstract::Pertussis or whooping cough, mainly caused by Bordetella pertussis, is a severe respiratory disease that can affect all age groups but is most severe and can be life-threatening in young children. Vaccines against this disease are widely available since the 1950s. Despite high global vaccination coverage, the disease ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.03068

    authors: Solans L,Locht C

    更新日期:2019-01-14 00:00:00

  • Immune Checkpoints as Therapeutic Targets in Autoimmunity.

    abstract::Antibodies that block the immune checkpoint receptors PD1 and CTLA4 have revolutionized the treatment of melanoma and several other cancers, but in the process, a new class of drug side effect has emerged-immune related adverse events. The observation that therapeutic blockade of these inhibitory receptors is sufficie...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02306

    authors: Paluch C,Santos AM,Anzilotti C,Cornall RJ,Davis SJ

    更新日期:2018-10-08 00:00:00

  • The Non-Obese Diabetic Mouse Strain as a Model to Study CD8(+) T Cell Function in Relapsing and Progressive Multiple Sclerosis.

    abstract::Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on central nervous system (CNS) myelin. Although CD4(+) T cell function in MS pathology has been extensively studied, there is also strong evidence that CD8(+) T lymphocytes play a key role. Intriguingly, CD8(+) T cells accumula...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00541

    authors: Ignatius Arokia Doss PM,Roy AP,Wang A,Anderson AC,Rangachari M

    更新日期:2015-10-22 00:00:00

  • Monkeying Around: Using Non-human Primate Models to Study NK Cell Biology in HIV Infections.

    abstract::Natural killer (NK) cells are the major innate effectors primed to eliminate virus-infected and tumor or neoplastic cells. Recent studies also suggest nuances in phenotypic and functional characteristics among NK cell subsets may further permit execution of regulatory and adaptive roles. Animal models, particularly no...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01124

    authors: Manickam C,Shah SV,Nohara J,Ferrari G,Reeves RK

    更新日期:2019-05-22 00:00:00

  • Beyond IgE-When Do IgE-Crosslinking and Effector Cell Activation Lead to Clinical Anaphylaxis?

    abstract::Anaphylaxis in humans is inherently difficult to study due to the acuteness of symptoms and the lack of biomarkers serving as risk predictors. Most cases are related to IgE sensitizations to foods, insect venoms, and drugs with mastocytosis patients forming a smaller risk group. However, identifying the relatively sma...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00871

    authors: Poulsen LK,Jensen BM,Esteban V,Garvey LH

    更新日期:2017-08-10 00:00:00

  • Controlling the Immune Suppressor: Transcription Factors and MicroRNAs Regulating CD73/NT5E.

    abstract::The NT5E (CD73) molecule represents an ecto-5'-nucleotidase expressed on the cell surface of various cell types. Hydrolyzing extracellular adenosine monophosphate into adenosine and inorganic phosphate, NT5E performs numerous homeostatic functions in healthy organs and tissues. Importantly, NT5E can act as inhibitory ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.00813

    authors: Kordaß T,Osen W,Eichmüller SB

    更新日期:2018-04-18 00:00:00

  • Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis.

    abstract::The dual potential to promote tolerance or inflammation to self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of dopamine receptor D5 (DRD5) in DCs potentiates their inflammatory behaviour, favouring the development of experimental autoimmune enc...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00571

    authors: Prado C,Gaiazzi M,González H,Ugalde V,Figueroa A,Osorio-Barrios FJ,López E,Lladser A,Rasini E,Marino F,Zaffaroni M,Cosentino M,Pacheco R

    更新日期:2018-03-21 00:00:00

  • Killer B lymphocytes and their fas ligand positive exosomes as inducers of immune tolerance.

    abstract::Induction of immune tolerance is a key process by which the immune system is educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding and harnessing the natural mechanisms of immune tolerance may become an increasingly useful strategy for treating many types of ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2015.00122

    authors: Lundy SK,Klinker MW,Fox DA

    更新日期:2015-03-20 00:00:00

  • Costimulatory Molecules and Immune Checkpoints Are Differentially Expressed on Different Subsets of Dendritic Cells.

    abstract::Dendritic cells (DCs) play a crucial role in initiating and shaping immune responses. The effects of DCs on adaptive immune responses depend partly on functional specialization of distinct DC subsets, and partly on the activation state of DCs, which is largely dictated by environmental signals. Fully activated immunos...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01325

    authors: Carenza C,Calcaterra F,Oriolo F,Di Vito C,Ubezio M,Della Porta MG,Mavilio D,Della Bella S

    更新日期:2019-06-11 00:00:00

  • Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development.

    abstract::PU.1 is an ETS-family transcription factor that plays a broad range of roles in hematopoiesis. A direct regulator of myeloid, dendritic-cell, and B cell functional programs, and a well-known antagonist of terminal erythroid cell differentiation, it is also expressed in the earliest stages of T-cell development of each...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00228

    authors: Rothenberg EV,Hosokawa H,Ungerbäck J

    更新日期:2019-02-20 00:00:00

  • Paired Rheumatoid Arthritis Synovial Biopsies From Small and Large Joints Show Similar Global Transcriptomic Patterns With Enrichment of Private Specificity TCRB and TCR Signaling Pathways.

    abstract:Objectives:We explored histological and transcriptomic profiles of paired synovial biopsies from rheumatoid arthritis (RA) patients, in order to assess homogeneity in synovial tissue at the individual level. Methods:Synovial biopsies were performed simultaneously in one small and one large joint per patient using need...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.593083

    authors: Triaille C,Vansteenkiste L,Constant M,Ambroise J,Méric de Bellefon L,Nzeusseu Toukap A,Sokolova T,Galant C,Coulie P,Carrasco J,Durez P,Lauwerys BR

    更新日期:2020-11-23 00:00:00

  • The where, when, how, and why of hyaluronan binding by immune cells.

    abstract::Hyaluronan is made and extruded from cells to form a pericellular or extracellular matrix (ECM) and is present in virtually all tissues in the body. The size and form of hyaluronan present in tissues are indicative of a healthy or inflamed tissue, and the interactions of hyaluronan with immune cells can influence thei...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00150

    authors: Lee-Sayer SS,Dong Y,Arif AA,Olsson M,Brown KL,Johnson P

    更新日期:2015-04-14 00:00:00

  • Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells.

    abstract::Mesenchymal stromal cells (MSCs) exert immunosuppressive effects on immune cells including dendritic cells (DCs). However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopon...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01207

    authors: Scutera S,Salvi V,Lorenzi L,Piersigilli G,Lonardi S,Alotto D,Casarin S,Castagnoli C,Dander E,D'Amico G,Sozzani S,Musso T

    更新日期:2018-06-01 00:00:00

  • Regulatory effects of C5a on IL-17A, IL-17F, and IL-23.

    abstract::The complement anaphylatoxin, C5a, through binding to its receptors (C5aR or C5L2), has important biological properties for recruitment and activation of phagocytes. C5a has been identified as a powerful modulator of Toll-like receptor-induced cytokine and chemokine production by macrophages. Both the complement syste...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00387

    authors: Grailer JJ,Bosmann M,Ward PA

    更新日期:2013-01-09 00:00:00

  • Role of innate immune response in non-alcoholic Fatty liver disease: metabolic complications and therapeutic tools.

    abstract::Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, both in adults and children. It is characterized by an aberrant lipid storage in hepatocytes, named hepatic steatosis. Simple steatosis remains a benign process in most affected patients, while some of them develop superimp...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00177

    authors: Meli R,Mattace Raso G,Calignano A

    更新日期:2014-04-23 00:00:00

  • Betaine Inhibits Interleukin-1β Production and Release: Potential Mechanisms.

    abstract::Betaine is a critical nutrient for mammal health, and has been found to alleviate inflammation by lowering interleukin (IL)-1β secretion; however, the underlying mechanisms by which betaine inhibits IL-1β secretion remain to be uncovered. In this review, we summarize the current understanding about the mechanisms of b...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02670

    authors: Xia Y,Chen S,Zhu G,Huang R,Yin Y,Ren W

    更新日期:2018-11-20 00:00:00

  • Indoleamine 2,3-Dioxygenase and Tolerance: Where Are We Now?

    abstract::Cells expressing IDO suppress innate and adaptive immunity to promote tolerance by catabolizing the amino acid tryptophan (Trp) and other indole compounds. Interferon type I (IFN-I) and type II (IFN-II) produced at sites of inflammation or by activated immune cells are potent IDO inducers because mammalian IDO genes c...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.01360

    authors: Mellor AL,Lemos H,Huang L

    更新日期:2017-10-27 00:00:00

  • MicroRNA Regulation of Host Immune Responses following Fungal Exposure.

    abstract::Fungal bioaerosols are ubiquitous in the environment and human exposure can result in a variety of health effects ranging from systemic, subcutaneous, and cutaneous infections to respiratory morbidity including allergy, asthma, and hypersensitivity pneumonitis. Recent research has focused on the role of microRNAs (miR...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.00170

    authors: Croston TL,Lemons AR,Beezhold DH,Green BJ

    更新日期:2018-02-07 00:00:00

  • Antimicrobial Proteins and Peptides in Early Life: Ontogeny and Translational Opportunities.

    abstract::While developing adaptive immune responses, young infants are especially vulnerable to serious infections, including sepsis, meningitis, and pneumonia. Antimicrobial proteins and peptides (APPs) are key effectors that function as broad-spectrum anti-infectives. This review seeks to summarize the clinically relevant fu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00309

    authors: Battersby AJ,Khara J,Wright VJ,Levy O,Kampmann B

    更新日期:2016-08-18 00:00:00

  • Vaccination with Altered Peptide Ligands of a Plasmodium berghei Circumsporozoite Protein CD8 T-Cell Epitope: A Model to Generate T Cells Resistant to Immune Interference by Polymorphic Epitopes.

    abstract::Many pathogens, including the malaria parasite Plasmodium falciparum, display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell ep...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00115

    authors: Minigo G,Flanagan KL,Slattery RM,Plebanski M

    更新日期:2017-02-14 00:00:00

  • Donor Genotype in the Interleukin-7 Receptor α-Chain Predicts Risk of Graft-versus-Host Disease and Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation.

    abstract::The efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute and chronic graft-versus-host disease (aGVHD and cGVHD) and viral infections due to long-lasting immunodeficiency. Interleukin-7 (IL-7) is a cytokine essential for de novo T cell generation in thymus and peripheral T cell ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00109

    authors: Kielsen K,Enevold C,Heilmann C,Sengeløv H,Pedersen AE,Ryder LP,Müller K

    更新日期:2018-02-02 00:00:00

  • Caveolin-1 Controls Vesicular TLR2 Expression, p38 Signaling and T Cell Suppression in BCG Infected Murine Monocytic Myeloid-Derived Suppressor Cells.

    abstract::Monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic MDSCs (G-MDSCs) have been found to be massively induced in TB patients as well in murine Mtb infection models. However, the interaction of mycobacteria with MDSCs and its role in TB infection is not well studied. Here, we investigated the role of Ca...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02826

    authors: John V,Kotze LA,Ribechini E,Walzl G,Du Plessis N,Lutz MB

    更新日期:2019-12-03 00:00:00