Search results for: Anthony L. DeFranco

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Dendritic Cell Expression of the Signaling Molecule TRAF6 Is Critical for Gut Microbiota-Dependent Immune Tolerance

Daehee Han, Matthew C. Walsh, Pedro J. Cejas, Nicholas N. Dang, more

Immunity > 2013 > 38 > 6 > 1211-1222

The intracellular signaling molecule TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). We now report that DC-specific deletion of TRAF6 (TRAF6ΔDC) resulted, unexpectedly, in loss of mucosal tolerance, characterized by spontaneous development of T helper 2 (Th2) cells in the lamina propria and eosinophilic enteritis and fibrosis in the small intestine. Loss...

article

Contribution of Toll‐like receptor signaling to germinal center antibody responses

Anthony L. DeFranco, Derek C. Rookhuizen, Baidong Hou

Immunological Reviews > 247 > 1 > 64 - 72

Summary: Toll‐like receptors (TLRs) have emerged as one of the most important families of innate immune receptors for initiating inflammation and also for promoting adaptive immune responses. Recent studies have examined the ability of TLRs to promote antibody responses, including T‐cell‐dependent antibody responses. Initial study suggested that TLR stimulation promotes primarily an extrafollicular...

article

B Cell-Intrinsic MyD88 Signaling Prevents the Lethal Dissemination of Commensal Bacteria during Colonic Damage

Donna Kirkland, Alicia Benson, Julie Mirpuri, Reed Pifer, more

Immunity > 2012 > 36 > 2 > 228-238

The Toll-like receptor adaptor protein MyD88 is essential for the regulation of intestinal homeostasis in mammals. In this study, we determined that Myd88-deficient mice are susceptible to colonic damage that is induced by dextran sulfate sodium (DSS) administration resulting from uncontrolled dissemination of intestinal commensal bacteria. The DSS-induced mortality of Myd88-deficient mice was completely...

article

Lyn deficiency affects B‐cell maturation as well as survival

Gitit Shahaf, Andrew J. Gross, Michal Sternberg‐Simon, Deborah Kaplan, more

European Journal of Immunology > 42 > 2 > 511 - 521

Lyn, an Src‐family protein tyrosine kinase expressed in B lymphocytes, contributes to initiation of BCR signaling and is also responsible for feedback inhibition of BCR signaling. Lyn‐deficient mice have a decreased number of follicular B cells and also spontaneously develop a lupus‐like autoimmunity. We used flow cytometric analysis, BrdU labeling and our mathematical models of B‐cell population...

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Elevated BCR signaling and decreased survival of Lyn‐deficient transitional and follicular B cells

Andrew J. Gross, Irina Proekt, Anthony L. DeFranco

European Journal of Immunology > 41 > 12 > 3645 - 3655

The Src‐family tyrosine kinase Lyn negatively regulates BCR signaling and also myeloid cell activity. Mice deficient in Lyn have substantially decreased numbers of peripheral B cells, despite spontaneously producing IgG anti‐DNA antibodies. Here, we examine the mechanism underlying the B‐cell depletion in these mice. Lyn‐deficient B cells were out‐competed by WT B cells in mixed BM chimeras at two...

article

Selective Utilization of Toll-like Receptor and MyD88 Signaling in B Cells for Enhancement of the Antiviral Germinal Center Response

Baidong Hou, Philippe Saudan, Gary Ott, Matthew L. Wheeler, more

Immunity > 2011 > 34 > 3 > 375-384

The contribution of Toll-like receptor (TLR) signaling to T cell-dependent (TD) antibody responses was assessed by using mice lacking the TLR signaling adaptor MyD88 in individual cell types. When a soluble TLR9 ligand was used as adjuvant for a protein antigen, MyD88 was required in dendritic cells but not in B cells to enhance the TD antibody response, regardless of the inherent immunogenicity of...

article

Unaltered negative selection and Treg development of self‐reactive thymocytes in TCR transgenic Fyn‐deficient mice

Alusha A. Mamchak, Christine B. F. Thien, Samantha A. Dagger, Julia Lyandres, more

European Journal of Immunology > 40 > 2 > 539 - 547

The tyrosine kinase Fyn has been implicated as playing an important role in the generation of both stimulatory and inhibitory signaling events induced by TCR engagement. To assess the role of Fyn for antigen‐driven negative selection and Treg development, which are both dependent on the strength and nature of TCR signaling, we generated mice that co‐express the transgenes for OVA and the OT‐II TCR,...

article

“Dangerous Crystals”

Anthony L. DeFranco

Immunity > 2008 > 29 > 5 > 670-671

Uric acid (UA) crystals are a potent stimulator of inflammation, but how they activate immune cells is not known. In this issue of Immunity, Ng et al. (2008) provide evidence suggesting that UA activates the Syk kinase via membrane cholesterol.

article

Toll-like Receptors Activate Innate and Adaptive Immunity by using Dendritic Cell-Intrinsic and -Extrinsic Mechanisms

Baidong Hou, Boris Reizis, Anthony L. DeFranco

Immunity > 2008 > 29 > 2 > 272-282

Toll-like receptors (TLRs) play prominent roles in initiating immune responses to infection, but their roles in particular cell types in vivo are not established. Here we report the generation of mice selectively lacking the crucial TLR-signaling adaptor MyD88 in dendritic cells (DCs). In these mice, the early production of inflammatory cytokines, especially IL-12, was substantially reduced after...

article

Lipid rafts and B cell signaling

Neetu Gupta, Anthony L. DeFranco

Seminars in Cell and Developmental Biology > 2007 > 18 > 5 > 616-626

B cells comprise an essential component of the humoral immune system. They are equipped with the unique ability to synthesize and secrete pathogen-neutralizing antibodies, and share with professional antigen presenting cells the ability to internalize foreign antigens, and process them for presentation to helper T cells. Recent evidence indicates that specialized cholesterol- and glycosphingolipid-rich...

article

Making and breaking tolerance

Pamela S. Ohashi, Anthony L. DeFranco

Current Opinion in Immunology > 2002 > 14 > 6 > 744-759

The lymphocyte's decision between tolerance and immunity/autoimmunity is regulated at many levels. Two important parameters in this decision are the maturation state of the antigen presenting cells (APCs) and the amount of self antigen that is detected by the immune system. Maturation of APCs occurs as a consequence of signals received by the innate immune system and may lead to the breakdown of tolerance...

article

Lupus-like kidney disease in mice deficient in the Src family tyrosine kinases Lyn and Fyn

Calvin C.K. Yu, T.S.Benedict Yen, Clifford A. Lowell, Anthony L. DeFranco

Current Biology > 2001 > 11 > 1 > 34-38

Systemic lupus erythematosus (SLE) is an autoimmune disease whose cause is poorly understood. Mice rendered deficient in specific genes have served as useful animal models in deciphering the genetic control of the disease [1]. We [2] and others [3, 4] previously demonstrated that mice deficient in the Src family tyrosine kinase Lyn developed a mild lupus-like disease with high survival rates. During...

article

CD19 Regulates Src Family Protein Tyrosine Kinase Activation in B Lymphocytes through Processive Amplification

Manabu Fujimoto, Yoko Fujimoto, Jonathan C Poe, Paul J Jansen, more

Immunity > 2000 > 13 > 1 > 47-57

CD19 regulates constitutive and antigen receptor–induced signaling thresholds in B lymphocytes through its unique cytoplasmic domain. Herein, we demonstrate a novel molecular mechanism where interactions between CD19 and Lyn amplify basal and antigen receptor–induced Src family kinase activation. Lyn expression was required for CD19 tyrosine phosphorylation in primary B cells. Experiments with purified...

article

Positive and negative roles of the tyrosine kinase Lyn in B cell function

Anthony L. DeFranco, Vivien W.F. Chan, Clifford A. Lowell

Seminars in Immunology > 1998 > 10 > 4 > 299-307

The function of Lyn in B cell activation has been studied recently by examining the properties of B cells from mice in which thelyngene has been inactivated by gene targeting. These mice show evidence of B cell hyperreactivityin vivo,as the number of B lymphoblastoid cells greatly increase with age, IgM levels increase by 10-fold or more, and auto- antibodies to double-stranded DNA and other nuclear...

article

Lymphocyte activation and effector functions Turning lymphocytes on and off

Anthony L DeFranco, Arthur Weiss

Current Opinion in Immunology > 1998 > 10 > 3 > 243-244

article

Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes

Vivien W.F. Chan, Clifford A. Lowell, Anthony L. DeFranco

Current Biology > 1998 > 8 > 10 > 545-553

Background: To elucidate the role of the Src family kinase Lyn in B cell receptor (BCR) signaling, we and others previously generated lyn ^−/− mice and analyzed their B cell responses. Although the initiation of BCR signaling in lyn ^−/− B cells is delayed, BCR-induced ERK2 activation and proliferation are enhanced. As the co-receptors FcγRIIb1 and CD22 have been shown to be negative...

article

Characterization of the B Lymphocyte Populations in Lyn-Deficient Mice and the Role of Lyn in Signal Initiation and Down-Regulation

Vivien W. F. Chan, Fanying Meng, Philippe Soriano, Anthony L. DeFranco, more

Immunity > 1997 > 7 > 1 > 69-81

Lyn-deficient mice were generated to analyze the role of Lyn in B cell antigen receptor (BCR) signaling. These mice had a reduced number of peripheral B cells with a greater proportion of immature cells and a higher than normal turnover rate. Aged lyn ^- ^/ ^- mice developed splenomegaly, produced autoantibodies, and had an expanded population of B lymphoblasts of the B1 lineage. Splenic...

article

The complexity of signaling pathways activated by the BCR

Anthony L DeFranco

Current Opinion in Immunology > 1997 > 9 > 3 > 296-308

Cross-linking of the B cell antigen receptor (BCR) leads to the activation of three types of intracellular protein tyrosine kinases. These tyrosine kinases then phosphorylate signaling components to activate a variety of signaling reactions, including phosphatidylinositol 4,5-bisphosphate hydrolysis, Ras activation, and phosphatidylinositol 3-kinase activation. Each of these signaling reactions, and...

article

B-cell co-receptors: The two-headed antigen

Anthony L DeFranco

Current Biology > 1996 > 6 > 5 > 548-550

Lymphocytes often recognize antigens using not only their antigen receptors but also ‘co-receptors’ that bind other molecules associated with the antigen; the co-receptors then modulate the response to antigen. This concept has been used to make chimeric antigens that are extremely potent inducers of antibody responses.

article

Assembly of the Truncated Immunoglobulin Heavy Chain Dμ into Antigen Receptor-Like Complexes in Pre-B Cells but Not in B Cells

Mary C. Horne, Patricia E. Roth, Anthony L. DeFranco

Immunity > 1996 > 4 > 2 > 145-158

Rearrangements of the IgH locus with J _H joined to reading frame 2 of D _H are greatly underrepresented in B cells. These rearrangements encode the truncated heavy chain Dμ. In pre-B cells, we found Dμ protein expressed on the cell surface and assembled into a complex with surrogate light chains, Igα, and Igβ. Cross-linking of either μm- or Dμm-containing pre-B cell receptors triggered...

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INFONA - science communication portal

Search results for: Anthony L. DeFranco

Dendritic Cell Expression of the Signaling Molecule TRAF6 Is Critical for Gut Microbiota-Dependent Immune Tolerance

Contribution of Toll‐like receptor signaling to germinal center antibody responses

B Cell-Intrinsic MyD88 Signaling Prevents the Lethal Dissemination of Commensal Bacteria during Colonic Damage

Lyn deficiency affects B‐cell maturation as well as survival

Elevated BCR signaling and decreased survival of Lyn‐deficient transitional and follicular B cells

Selective Utilization of Toll-like Receptor and MyD88 Signaling in B Cells for Enhancement of the Antiviral Germinal Center Response

Unaltered negative selection and Treg development of self‐reactive thymocytes in TCR transgenic Fyn‐deficient mice

“Dangerous Crystals”

Toll-like Receptors Activate Innate and Adaptive Immunity by using Dendritic Cell-Intrinsic and -Extrinsic Mechanisms

Lipid rafts and B cell signaling

Making and breaking tolerance

Lupus-like kidney disease in mice deficient in the Src family tyrosine kinases Lyn and Fyn

CD19 Regulates Src Family Protein Tyrosine Kinase Activation in B Lymphocytes through Processive Amplification

Positive and negative roles of the tyrosine kinase Lyn in B cell function

Lymphocyte activation and effector functions Turning lymphocytes on and off

Defective negative regulation of antigen receptor signaling in Lyn-deficient B lymphocytes

Characterization of the B Lymphocyte Populations in Lyn-Deficient Mice and the Role of Lyn in Signal Initiation and Down-Regulation

The complexity of signaling pathways activated by the BCR

B-cell co-receptors: The two-headed antigen

Assembly of the Truncated Immunoglobulin Heavy Chain Dμ into Antigen Receptor-Like Complexes in Pre-B Cells but Not in B Cells

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