Dysregulated TRAF3 and BCL2 Expression Promotes Multiple Classes of Mature Non-hodgkin B Cell Lymphoma in Mice.


:TNF-Receptor Associated Factor (TRAF)-3 is a master regulator of B cell homeostasis and function. TRAF3 has been shown to bind and regulate various proteins involved in the control of innate and adaptive immune responses. Previous studies showed that TRAF3 overexpression renders B cells hyper-reactive to antigens and Toll-like receptor (TLR) agonists, while TRAF3 deficiency has been implicated in the development of a variety of B cell neoplasms. In this report, we show that transgenic mice overexpressing TRAF3 and BCL2 in B cells develop with high incidence severe lymphadenopathy, splenomegaly and lymphoid infiltrations into tissues and organs, which is the result of the growth of monoclonal and oligoclonal B cell neoplasms, as demonstrated by analysis of VHDJH gene rearrangement. FACS and immunohistochemical analyses show that different types of mature B cell neoplasms arise in TRAF3/BCL2 double-transgenic (tg) mice, all of which are characterized by the loss of surface IgM and IgD expression. However, two types of lymphomas are predominant: (1) mature B cell neoplasms consistent with diffuse large B cell lymphoma and (2) plasma cell neoplasms. The Ig isotypes expressed by the expanded B-cell clones included IgA, IgG, and IgM, with most having undergone somatic hypermutation. In contrast, mouse littermates representing all the other genotypes (TRAF3-/BCL2-; TRAF3+/BCL2-, and TRAF3-/BCL2+) did not develop significant lymphadenopathy or clonal B cell expansions within the observation period of 20 months. Interestingly, a large representation of the HCDR3 sequences expressed in the TRAF3-tg and TRAF3/BCL2-double-tg B cells are highly similar to those recognizing pathogen-associated molecular patterns and damage-associated molecular patterns, strongly suggesting a role for TRAF3 in promoting B cell differentiation in response to these antigens. Finally, allotransplantation of either splenocytes or cell-containing ascites from lymphoma-bearing TRAF3/BCL2 mice into SCID/NOD immunodeficient mice showed efficient transfer of the parental expanded B-cell clones. Altogether, these results indicate that TRAF3, perhaps by promoting exacerbated B cell responses to certain antigens, and BCL2, presumably by supporting survival of these clones, cooperate to induce mature B cell neoplasms in transgenic mice.


Front Immunol


Frontiers in immunology


Perez-Chacon G,Adrados M,Vallejo-Cremades MT,Lefebvre S,Reed JC,Zapata JM




Has Abstract


2019-01-11 00:00:00








  • Parallels in Immunometabolic Adipose Tissue Dysfunction with Ageing and Obesity.

    abstract::Ageing, like obesity, is often associated with alterations in metabolic and inflammatory processes resulting in morbidity from diseases characterised by poor metabolic control, insulin insensitivity, and inflammation. Ageing populations also exhibit a decline in immune competence referred to as immunosenescence, which...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Trim W,Turner JE,Thompson D

    更新日期:2018-02-09 00:00:00

  • ERdj5 in Innate Immune Cells Is a Crucial Factor for the Mucosal Adjuvanticity of Cholera Toxin.

    abstract::Cholera toxin (CT) is one of most strong mucosal adjuvants, but it cannot be clinically used owing to its toxicity. The cytosolic A1 subunit of CT (CTA1) is the molecule responsible for its immunostimulatory activity, which increases the concentration of cyclic AMP and causes the induction of pro-inflammatory cytokine...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Kim MS,Yi EJ,Kim YI,Kim SH,Jung YS,Kim SR,Iwawaki T,Ko HJ,Chang SY

    更新日期:2019-06-04 00:00:00

  • A Novel Synthetic Dual Agonistic Liposomal TLR4/7 Adjuvant Promotes Broad Immune Responses in an Influenza Vaccine With Minimal Reactogenicity.

    abstract::The limited efficacy of seasonal influenza vaccines is usually attributed to ongoing variation in the major antigenic targets for protective antibody responses including hemagglutinin (HA) and neuraminidase (NA). Hence, vaccine development has largely focused on broadening antigenic epitopes to generate cross-reactive...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Sato-Kaneko F,Yao S,Lao FS,Shpigelman J,Messer K,Pu M,Shukla NM,Cottam HB,Chan M,Chu PJ,Burkhart D,Schoener R,Matsutani T,Carson DA,Corr M,Hayashi T

    更新日期:2020-06-19 00:00:00

  • The impact of HIV-1 infection and exposure on natural killer (NK) cell phenotype in Kenyan infants during the first year of life.

    abstract::Natural killer (NK) cells play an important role in the containment of HIV replication during primary infection, though their functions are impaired during chronic HIV infection. Infants experience more rapid HIV disease progression than adults, but contributions of infant NK cells to containing HIV infection are unkn...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Slyker JA,Lohman-Payne B,John-Stewart GC,Dong T,Mbori-Ngacha D,Tapia K,Atzberger A,Taylor S,Rowland-Jones SL,Blish CA

    更新日期:2012-12-31 00:00:00

  • IL-22: An Underestimated Player in Natural Resistance to Tuberculosis?

    abstract::Approximately 10% of individuals latently infected with Mycobacterium tuberculosis (Mtb) develop active tuberculosis (TB) during their lifetime. Although it is well recognized that T-helper 1 immune responses are crucial for containing latent TB infection, the full array of host factors conferring protective immunity ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Ronacher K,Sinha R,Cestari M

    更新日期:2018-09-25 00:00:00

  • Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer's Disease Brain.

    abstract::Abundant clinical, epidemiological, imaging, genetic, molecular, and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer's disease (AD) brain. Despite many years of intense study, the origin and molecular mechan...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Zhao Y,Cong L,Jaber V,Lukiw WJ

    更新日期:2017-09-04 00:00:00

  • IL-10 and IL-22 in Mucosal Immunity: Driving Protection and Pathology.

    abstract::The barrier surfaces of the gastrointestinal tract are in constant contact with various microorganisms. Cytokines orchestrate the mucosal adaptive and innate immune cells in the defense against pathogens. IL-10 and IL-22 are the best studied members of the IL-10 family and play essential roles in maintaining mucosal h...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Wei HX,Wang B,Li B

    更新日期:2020-06-26 00:00:00

  • Age-Based Dynamics of a Stable Circulating Cd8 T Cell Repertoire Component.

    abstract::T-cell memory to pathogens can be envisioned as a receptor-based imprint of the pathogenic environment on the naïve repertoire of clonotypes. Recurrent exposures to a pathogen inform and reinforce memory, leading to a mature state. The complexity and temporal stability of this system in man is only beginning to be ade...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Naumova EN,Yassai MB,Demos W,Reed E,Unruh M,Haribhai D,Williams CB,Naumov YN,Gorski J

    更新日期:2019-08-06 00:00:00

  • Dermatomyositis and Immune-Mediated Necrotizing Myopathies: A Window on Autoimmunity and Cancer.

    abstract::Autoimmune myopathies (myositides) are strongly associated with malignancy. The link between myositis and cancer, originally noticed by Bohan and Peter in their classification in 1975 (1), has been evidenced by large population-based cohort studies and a recent meta-analysis. The numerous reports of cases in which the...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Aussy A,Boyer O,Cordel N

    更新日期:2017-08-21 00:00:00

  • Innate Immune Cells' Contribution to Systemic Lupus Erythematosus.

    abstract::Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies against nuclear antigens, immune complex deposition, and tissue damage in the kidneys, skin, heart and lung. Because of the pathogenic role of antinuclear antibodies and autoreactive T cells in SLE, exten...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Herrada AA,Escobedo N,Iruretagoyena M,Valenzuela RA,Burgos PI,Cuitino L,Llanos C

    更新日期:2019-04-15 00:00:00

  • Therapeutic implications of immunogenic cell death in human cancer.

    abstract::Dendritic cells (DCs) are central to the adoptive immune response, and their function is regulated by diverse signals in a context-specific manner. Different DCs have been described in physiologic conditions, inflammation, and cancer, prompting a series of questions on how adoptive immune responses, or tolerance, deve...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Palombo F,Focaccetti C,Barnaba V

    更新日期:2014-01-06 00:00:00

  • Human Endogenous Retroviruses Are Ancient Acquired Elements Still Shaping Innate Immune Responses.

    abstract::About 8% of our genome is composed of sequences with viral origin, namely human Endogenous Retroviruses (HERVs). HERVs are relics of ancient infections that affected the primates' germ line along the last 100 million of years, and became stable elements at the interface between self and foreign DNA. Intriguingly, HERV...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Grandi N,Tramontano E

    更新日期:2018-09-10 00:00:00

  • Predictive Biomarkers of Immune Checkpoint Inhibitors-Related Toxicities.

    abstract::The emergence and continuous development of immune checkpoint inhibitors (ICIs) therapy brings a revolution in cancer therapy history, but the major hurdle associated with their usage is the concomitant ICIs-related toxicities that present a challenge for oncologists. The toxicities may involve non-specific symptoms o...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Xu Y,Fu Y,Zhu B,Wang J,Zhang B

    更新日期:2020-10-06 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


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

    更新日期:2018-02-07 00:00:00

  • Uncovering Low-Level Maternal Gonosomal Mosaicism in X-Linked Agammaglobulinemia: Implications for Genetic Counseling.

    abstract::X-linked agammaglobulinemia (XLA) is a clinically and genetically well-defined immunodeficiency and the most common form of agammaglobulinemia. It is characterized by susceptibility to recurrent bacterial infections, profound hypogammaglobulinemia, and few or no circulating B cells. XLA is caused by mutations in the B...

    journal_title:Frontiers in immunology



    authors: Rivière JG,Franco-Jarava C,Martínez-Gallo M,Aguiló-Cucurull A,Blasco-Pérez L,Paramonov I,Antolín M,Martín-Nalda A,Soler-Palacín P,Colobran R

    更新日期:2020-02-12 00:00:00

  • Regulation of immune reactivity by intercellular transfer.

    abstract::It was recently proposed that T lymphocytes, which closely interact with APCs, can extract surface molecules from the presenting cells when they dissociate. These observations question the classical view of discrete interactions between phenotypically defined cell populations. In this review, we summarize some reports...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Dhainaut M,Moser M

    更新日期:2014-03-28 00:00:00

  • Immunomodulation by IVIg and the Role of Fc-Gamma Receptors: Classic Mechanisms of Action after all?

    abstract::Intravenous IgG (IVIg) contains polyclonal immunoglobulin G (IgG) from thousands of donors. It is administered at a low dose at regular intervals as antibody replacement therapy and at a higher dose as immunomodulatory treatment in various auto-immune or auto-inflammatory diseases. The working mechanism of immunomodul...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Nagelkerke SQ,Kuijpers TW

    更新日期:2015-01-21 00:00:00

  • Genetic Diversity of Human Rotavirus A Among Hospitalized Children Under-5 Years in Lebanon.

    abstract::Human rotavirus remains a major cause of gastroenteritis worldwide despite the availability of effective vaccines. In this study, we investigated the genetic diversity of rotaviruses circulating in Lebanon. We genetically characterized the VP4 and VP7 genes encoding the outer capsid proteins of 132 rotavirus-associate...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Harastani HH,Reslan L,Sabra A,Ali Z,Hammadi M,Ghanem S,Hajar F,Matar GM,Dbaibo GS,Zaraket H

    更新日期:2020-02-26 00:00:00

  • Sedimentation Velocity Analytical Ultracentrifugation of Oxidized Recombinant Full-Length Factor VIII.

    abstract::Anti-drug antibodies to coagulation factor VIII (fVIII), often termed inhibitors, present the greatest economical and treatment related obstacle in the management of hemophilia A. Although several genetic and environmental risk factors associated with inhibitor development have been identified, the precise mechanisms ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Zakas PM,Healey JF,Smith IW,Lillicrap D,Lollar P

    更新日期:2020-02-07 00:00:00

  • Alkaline pH Promotes NADPH Oxidase-Independent Neutrophil Extracellular Trap Formation: A Matter of Mitochondrial Reactive Oxygen Species Generation and Citrullination and Cleavage of Histone.

    abstract::pH is highly variable in different tissues and affects many enzymatic reactions in neutrophils. In response to calcium ionophores such as A23187 and ionomycin, neutrophils undergo nicotinamide adenine dinucleotide phosphate oxidase (NOX)-independent neutrophil extracellular trap (NET) formation (NETosis). However, how...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Naffah de Souza C,Breda LCD,Khan MA,de Almeida SR,Câmara NOS,Sweezey N,Palaniyar N

    更新日期:2018-01-09 00:00:00

  • Stressful presentations: mild cold stress in laboratory mice influences phenotype of dendritic cells in naïve and tumor-bearing mice.

    abstract::The ability of dendritic cells (DCs) to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to model im...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Kokolus KM,Spangler HM,Povinelli BJ,Farren MR,Lee KP,Repasky EA

    更新日期:2014-02-10 00:00:00

  • The Role of the Immune Response in Chlamydia trachomatis Infection of the Male Genital Tract: A Double-Edged Sword.

    abstract::Chlamydia trachomatis (CT) is the most prevalent bacterial sexually transmitted infection in the world, with more than 100 million cases reported annually. While there have been extensive studies into the adverse effects that CT infection has on the female genital tract, and on the subsequent ability of these women to...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Redgrove KA,McLaughlin EA

    更新日期:2014-10-27 00:00:00

  • Therapeutic Targeting of Neutrophil Granulocytes in Inflammatory Liver Disease.

    abstract::Neutrophil granulocytes are the most numerous type of leukocyte in humans bearing an enormous, yet largely unexplored therapeutic potential. Scientists have very recently increased their efforts to study and understand these cells which contribute to various types of inflammatory diseases and cancer. The mechanisms th...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Bartneck M,Wang J

    更新日期:2019-09-20 00:00:00

  • The Interplay Between Monocytes/Macrophages and CD4(+) T Cell Subsets in Rheumatoid Arthritis.

    abstract::Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation of the synovial lining (synovitis). The inflammation in the RA joint is associated with and driven by immune cell infiltration, synovial hyperproliferation, and excessive production of proinflammatory mediators, such as tumor nec...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Roberts CA,Dickinson AK,Taams LS

    更新日期:2015-11-19 00:00:00

  • Glucocorticoids Shape Macrophage Phenotype for Tissue Repair.

    abstract::Inflammation is a complex process which is highly conserved among species. Inflammation occurs in response to injury, infection, and cancer, as an allostatic mechanism to return the tissue and to return the organism back to health and homeostasis. Excessive, or chronic inflammation is associated with numerous diseases...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Desgeorges T,Caratti G,Mounier R,Tuckermann J,Chazaud B

    更新日期:2019-07-09 00:00:00

  • Mesothelioma in Familial Mediterranean Fever With Colchicine Intolerance: A Case Report and Literature Review.

    abstract::A 65-year-old Italian physician affected by Familial Mediterranean fever (FMF) was hospitalized due to progressive abdominal enlargement, which had begun 6 months before admission. Physical examination revealed ascites and bilateral leg edema. Abdominal CT scan showed ascitic fluid and extensive multiple peritoneal im...

    journal_title:Frontiers in immunology



    authors: Talerico R,Cardillo C,De Vito F,Schinzari F,Soldato M,Giustiniani MC,Verrecchia E,Manna R

    更新日期:2020-05-13 00:00:00

  • Increased Binding of Specificity Protein 1 to the IL21R Promoter in B Cells Results in Enhanced B Cell Responses in Rheumatoid Arthritis.

    abstract::B cells are implicated in rheumatoid arthritis (RA) based on the presence of autoantibodies and the therapeutic response to B cell depletion. IL-21 has a significant role in B cell development and function. Here we assess B cell responses to IL-21 and the mechanisms responsible for altered IL-21R expression in RA. Flo...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Dam EM,Maier AC,Hocking AM,Carlin J,Ng B,Buckner JH

    更新日期:2018-09-05 00:00:00

  • IL-1 family cytokines trigger sterile inflammatory disease.

    abstract::Inflammation plays vital roles in protective responses against pathogens and tissue repair, however, improper resolution of inflammatory networks is centrally involved in the pathogenesis of many acute and chronic diseases. Extensive advances have been made in recent years to define the inflammatory processes that are...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Lukens JR,Gross JM,Kanneganti TD

    更新日期:2012-10-09 00:00:00

  • Retinoic Acid Mediated Clearance of Citrobacter rodentium in Vitamin A Deficient Mice Requires CD11b+ and T Cells.

    abstract::Vitamin A deficiency affects over 250 million preschool-age children worldwide and is associated with increased childhood mortality and risk of developing enteric infections. Vitamin A deficient (A-) mice developed chronic Citrobacter rodentium infection. A single oral dose of retinoic acid (RA) at d7 post-infection w...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Snyder LM,McDaniel KL,Tian Y,Wei CH,Kennett MJ,Patterson AD,Ross AC,Cantorna MT

    更新日期:2019-01-08 00:00:00

  • Achievement of Tolerance Induction to Prevent Acute Graft-vs.-Host Disease.

    abstract::Acute graft-vs.-host disease (GVHD) limits the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), a main therapy to treat various hematological disorders. Despite rapid progress in understanding GVHD pathogenesis, broad immunosuppressive agents are most often used to prevent and remain the fir...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Thangavelu G,Blazar BR

    更新日期:2019-03-06 00:00:00