MARCH1 : new insights in the activation of B cells

L’implication des cellules B dans le développement de l’auto-immunité ne cesse d’être illustrée par de récentes publications. Les cellules présentent des peptides du soi aux cellules T auto-réactives ce qui mène à la production de cytokines pro-inflammatoires et d’anticorps auto-réactifs. Dans le présent document, nous explorons la présentation antigénique et la modification post-traductionnelle du complexe majeur d’histocompatibilité II (CMH-II). MARCH1 est une E3 ubiquitine ligase qui cible le CMH-II et le relocalise le complexe vers les endosomes de recyclage. Ainsi, MARCH1 est un inhibiteur de la présentation d’antigènes exogènes. Ici, nous démontrons que MARCH1 est exprimé seulement dans la sous-population des cellules B folliculaires et que cette expression est perdue lors de l’entrée dans les centres germinatifs. Nous proposons que MARCH1 établie une barrière de formation de centres germinatifs. Nous démontrons le lien entre MARCH1 et la hausse de CMH-II à la surface des cellules B à la suite d’un traitement à l’IL-10. De plus, nous avons testé plusieurs stimuli activateurs des cellules B et démontrons que MARCH1 est régulé à la baisse dans tous les cas. De plus, nous mettons en valeurs le rôle de la voie canonique d’activation de NF-κB dans cette régulation de MARCH1. Finalement, nous avons développé un système de lentivirus exprimant MARCH1 qui nous permet de forcer l’expression de MARCH1 dans des cellules réfractaires à la transfection. Nous discutons de l’implication de cette régulation du CMH-II par MARCH1 dans le développement de maladies auto-immunes.

Explaining the Great Divergence: Medium and Message on the Eurasian Land Mass, 1700-1850

Between 1700 and 1850, per-capita income doubled in Europe while falling in the rest of Eurasia. Neither geography nor economic institutions can explain this sudden divergence. Here the consequences of differences in communications technology are examined. For the first time, there appeared in Europe a combination of a standardized medium (national vernaculars with a phonetic alphabet) and a non-standardized message (competing religious, political and scientific ideas). The result was an unprecedented fall in the cost of combining ideas and burst of productivity-raising innovation. Elsewhere, decreasing standardization of the medium and increasing standardization of the message blocked innovation.

The great asymmetry : America's closest allies in times of war

This dissertation focuses on military cooperation between the United States and its special allies. It argues that alliance expectations determine the level of military cooperation, while two intervening variables - the level of government cohesion and military capabilities - determine its implementation. This study also shows how secondary states deploy strategies to overcome power asymmetries through bilateral concessions, international organizations and by appealing to principle. The focus of the research is on special allies, as they have the most to gain or lose by going along with American plans. My contention is that secondary allies can rarely influence the dominant ally decisively, but they can act autonomously and resist to pressures exerted by the stronger alliance partner. The argument builds on three central claims. First, power asymmetries between allies translate into different assessments of international threats. Second, when disagreements over threats arise, the outcome of intra-alliance bargaining is not necessarily dictated by the preferences of the stronger power. Third, secondary states, as opposed to the dominant partner, face unique constraints when facing major foreign policy decisions, i.e. they face a trade-off between establishing a credible reputation as an alliance partner in a politically feasible way while minimizing domestic audience costs. To examine the theoretical puzzle presented by asymmetric military cooperation, I introduce a causal explanation that builds on neoclassical realism, to zone in on the interaction between systemic and domestic variables. My research makes a contribution to alliance theory and foreign policy decision-making by studying how special allies respond to American decisions in times of threat and how systemic constraints are channeled through state-level variables. To investigate the causal link between threat perception, alliance expectations and domestic constraints, this study relies on the method of structured focused comparison with three detailed case studies. The focus is on the initial decision made by special allies regarding whether or not to participle in joint mobilization with the United States. The decision-making process is presented from the perspective of secondary allied states and measures the explanatory factors that motivated the decision on military cooperation. The case studies are the UK, Canada and Australia’s response to the war in Afghanistan and the war in Iraq during the period of 2001 to 2003.

Baby-boom, baby-bust and the Great Depression

The baby-boom and subsequent baby-bust have shaped much of the history of the second half of the 20th century; yet it is still largely unclear what caused them. This paper presents a new unified explanation of the fertility Boom-Bust that links the latter to the Great Depression and the subsequent economic recovery. We show that the 1929 Crash attracted young married women 20 to 34 years old in 1930 (whom we name D-cohort) in the labor market possibly via an added worker effect. Using several years of Census micro data, we further document that the same cohort kept entering into the market in the 1940s and 1950s as economic conditions improved, decreasing wages and reducing work incentives for younger women. Its retirement in the late 1950s and in the 1960s instead freed positions and created employment opportunities. Finally, we show that the entry of the D-cohort is associated with increased births in the 1950s, while its retirement turned the fertility Boom into a Bust in the 1960s. The work behavior of this cohort explains a large share of the changes in both yearly births and completed fertility of all cohorts involved.