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Academic literature on the topic 'Commutation isotypique – Aspect moléculaire'
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Dissertations / Theses on the topic "Commutation isotypique – Aspect moléculaire"
Heyer, Vincent. "Étude de l'impact des facteurs induits par l'hypoxie sur l'expression de l'enzyme AID au cours du processus de commutation isotypique des immunoglobulines." Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ026.
Full textImmunoglobulins are produced by B lymphocytes, and the diversity found in the B cell repertoire arises from two major stages. The initial stage occurs during the development of B cells in the bone marrow, where the V(D)J recombination mechanism orchestrates the assembly of variable regions VH and VL. The second takes place during immune responses, facilitated by two distinct mechanisms: somatic hypermutation (SHM) and class switch recombination (CSR). Both CSR and SHM depend on the action of the enzyme AID (activation-induced cytidine deaminase). Despite its crucial role in humoral immunity, AID has significant oncogenic potential due to its ability to cause DNA damage outside of immunoglobulin loci. Identifying the regulatory proteins of AID allows a better understanding of how this balance is regulated. The approach of this project involves identifying proteins associated with AID through a proteomic methodology, isolating them through co-immunoprecipitation reactions, and identifying them using mass spectrometry. This research has led to the identification of over 300 proteins and the discovery and functional characterization of four important protein complexes crucial in AID regulation. It has been demonstrated that, during immune responses, hypoxic areas are observed within germinal centers (GC), and the response to hypoxia modulates the humoral response. My research has highlighted that the expression of AID and the efficiency of class switch recombination of immunoglobulins are conditioned by the hypoxia-inducible factor (HIF)
Malisan, Florence. "Étude moléculaire et cellulaire de la commutation isotypique des lymphocytes B humains in vivo et in vitro." Lyon 1, 1996. http://www.theses.fr/1996LYO1T004.
Full textPeron, Sophie. "Caractérisation moléculaire des déficits immunitaires héréditaires liés à un défaut de la commutation isotypique des immunoglobulines." Paris 7, 2008. http://www.theses.fr/2008PA077109.
Full textAntibody diversity generation occurs in two steps: the primary antibody repertoire is generated in the fetal liver and in the bone marrow by means of the v(d)j recombination process and the secondary antibody repertoire is shaped in secondary lymphoid organs. The terminal maturation of b lymphocytes occurs in the germinal centers of the secondary lymphoid organs following antigen (ag) and t-cell-driven activation. Two major events take place: class switch recombination (csr) resulting in the production of immunoglobulin (ig) of different isotypes and somatic hypermutations (shm). Defects in the terminal maturation of b cells result in ig-csr deficiencies. Ig-csr deficiencies are rare primary immunodeficiencies characterized by a defective ig-csr variably associated with defective shm. Activation-induced cytidine deaminase (aid) and uracil-n glycosylase (ung) deficiencies have established the major role of aid in antibody maturation. Meanwhile, most cases of intrinsic b-cell defects responsible for ig-csr deficiencies are not due to aid or ung deficiencies and are related to unknown molecular basis. The major aim of my thesis was to contribute to the molecular characterization of these immunodeficiencies. We have characterized two new ig-csr deficiencies: the first one is due to pms2 deficiency, the second is assosiated with defective dna repair. The ongoing delineation of inherited ig-csr deficiencies is essential from a medical point of view and contributes to a better understanding of the complex mechanisms underlying antibody maturation in humans
Asato, Ryosuke. "Design and synthesis of multifunctional terarylenes for mechano-, radio- and thermo-chemical responses." Thesis, Toulouse 3, 2021. http://www.theses.fr/2021TOU30005.
Full textMolecular switching materials that modulate physical properties through an external trigger have received much attention in the development of new devices. They require precise switching performance and large scale propagation on single and multiple molecular levels. Diarylethene has attracted much attention due to its excellent photoswitching properties. These molecules photocyclize from the open (o) form to the closed (c) form with UV light, with visible light inducing reversion to the o form. Terarylene structures have been optimized for switching in areas including photoreaction quantum yields, thermal stability and desorption of functional groups upon structural change. In this thesis the focus is placed upon a single photoswitching reaction and the affect this has on local geometry and physical properties. First, this thesis shows that a small number of photoswitching reactions on a terarylene subunit can stop or start dynamic movement, namely the rotation of a molecular motor. The rotation was activated depending on which part of the rotor is approached by an electron injecting STM tip; with light irradiation offering a second independent control input. A new motor containing a terarylene substituent was designed in which the flexible open form can be converted to its rigid closed form to block rotation via steric interactions thus acting as a light-induced brake. With the initial target unit for this motor chosen using computational calculations of these interactions. A new synthetic methodology for the introduction of the photoswiching unit into the motor is presented and then the rotational control was discussed using spectral changes in the NMR upon irradiation. In the second part of this thesis, the effect c to o form isomerization of terarylenes has on nearby molecules through synergetic effects are presented. Work to enhance the quantum yield of the isomerization provides new applications using alternative stimulus without light irradiation. Examples including chemical or electrochemical oxidation proceed with high efficiency in a (electro)catalytic way, with apparent reaction efficiency exceeding 100% through a cascade reaction. By introducing aromatic groups on the reactive carbons of a photoreactive system, the efficiency of the electrocatalytic cycloreversion reaction was increased to 100000% and applied to the amplified detection of a small amount of high energy photons such as X-rays. In the third part, new molecular solar thermal (MOST) fuel is presented using the cascade reaction. MOST fuel systems capture photonic energy, retaining photocurrent in the formed chemical bond, instead of battery based electrochemical storage. The high energy density of MOST fuel offers large heat release, with cycloreversion via bond disassociation at levels equivalent to artificial photosynthesis without environmental impact. A small amount of electrochemical or chemical oxidation can induce the cascade release of stored thermal energy. In addition, a storing process of the light energy optimized by introduction of phenyl rings on the terarylene reactive carbon atoms has been developed. These present high MOST efficiency and the results are supported by a detailed computational study
Leduc, Claire. "Impact de la délétion de TRRAP ou MSH2 sur le développement des cellules B et la commutation isotypique." Toulouse 3, 2009. http://thesesups.ups-tlse.fr/832/.
Full textTRRAP is a common component of histone-acetyltransferase (HAT) complexes. TRRAPalso takes part in MRN complexe, without any HAT activity. TRRAP is implicated in severalprocesses where DNA accessibility is required, such as transcription and DNA repair. Trrapdeletion in mouse results in embryonic lethality. To avoid this lethality, we took advantage ofthe Cre-LoxP system with Cre under the control of CD19 transcriptional regulatory elements;CD19 being only expressed in B cells. Phenotypic and molecular analyses of Trrap-/-/CD19Cre/Cre mice B cells demonstrated thatTRRAP is strongly implicated in B cell development and CSR. Analyses by single cell PCR at eachdevelopmental stage revealed that TRRAP is absolutely required for proliferation; Effects ofTRRAP deletion are more pronounced in proliferating cells than in quiescent cells. My resultsalso suggest that TRRAP plays a central role in cell cycle regulationMSH2 takes part in mismatch repair. Its precise role in CSR is still unknown althoughMSH2 deficiency results in slight reduction of CSR. Currently MSH2 is thought to be implicated indouble strand breaks (DSB) generated outside S regions tandem repeats during CSR. To test this model, I analyzed CSR in MSH2 and Sµ tandem repeats deficient mice. Analysis of those mutants shows a complete CSR abolishment. Neither S region transcription norcell proliferation (both required for CSR) are implicated. It seems likely that a lack of DSB isresponsible for the absence of CSR, despite AID hotspots presence. Besides, my resultsdemonstrate that MSH2 affects Sµ region but also domains outside R-loops