Physics Opportunities with the 12 GeV Upgrade at Jefferson Lab

This white paper summarizes the scientific opportunities for utilization of the upgraded 12 GeV Continuous Electron Beam Accelerator Facility (CEBAF) and associated experimental equipment at Jefferson Lab. It is based on the 52 proposals recommended for approval by the Jefferson Lab Program Advisory Committee.The upgraded facility will enable a new experimental program with substantial discovery potential to address important topics in nuclear, hadronic, and electroweak physics.Comment: 64 page

T lymphocytes from human chimeras do recognize antigen in the context of allogeneic determinants of the major histocompatibility complex

Human stem cells from the fetal liver can be transplanted to immunodeficient patients and reconstitute their immunity by giving rise to immunocompetent T lymphocytes of donor origin. Despite full HLA mismatch between donor and host, the helper T cells and the cytotoxic T cells which develop in these chimeric patients are totally functional. They recognize the antigenic peptides presented in the context of the foreign HLA molecules of the recipient, indicating that donor stem cells have been positively selected in the host environment, probably the thymic epithelial cells. By contrast, negative selection appears to be imposed upon T cells by donor hemopoietic cells, probably macrophages or dendritic cells, migrating from the transplant to the host thymus. Clonal deletion is then responsible for tolerance to donor HLA antigens, while clonal anergy explains tolerance to host HLA antigen

Human IG production and isotype switching in severe combined immunodeficient: human mice

Severe combined immunodeficient (SCID) mice were transplanted with different human fetal organs (SCID-hu mice), including thymus, liver, spleen, and omentum, and the serum levels of human IgM, IgG, IgE, and IgA were measured. In all SCID-hu mice significant levels (up to 590 ng/ml) of IgM were detected, irrespective of the organs transplanted. In contrast, IgG was present (up to 530 ng/ml) only when the fetal thymus was transplanted together with the fetal liver, indicating that the presence of human T cells is a prerequisite for in vivo isotype switching by human B cells in SCID-hu mice. Additional transplantation of fetal spleen did not significantly increase IgG levels. Human IgA and IgE were never detected in the serum of these SCID-hu mice. The peak of IgM and IgG production was observed 4 months after transplantation. At that time, analysis by IEF showed that human IgG present in SCID-hu serum was at least oligoclonal. Furthermore, all IgG subclasses were represented in the human IgG pool. Human B cells were undetectable in the peripheral blood, spleen, and bone marrow of-these SCID-hu mice; in contrast, B cells expressing CD19 could be isolated from the SCID-hu thymus. Considerable proportions of the CD19+ B cells coexpressed CD5, CD7, CD10, CD40, and CD2. These B cells spontaneously produced IgM and IgG in vitro and could be induced to switch to IgE-producing cells when cocultured with cloned activated CD4+ T cells in the presence of IL-4. Collectively, these data demonstrate that functionally mature B cells able to produce IgM and IgG in vivo, and IgE in vitro, are present in the SCID-hu human thymus

Caractérisation fonctionnelle de sept variations faux-sens dans le gène du récepteur sensible au calcium (CASR)

International audienceLe récepteur sensible au calcium (CaSR) est un RCPG qui régule l’homéostasie du calcium extracellulaire (Ca2+e), codé parle gène CASR. Cette régulation se fait par la mobilisation du calcium intracellulaire (Ca2+i) et la voie de signalisationMAPK. Les mutations du gène CASR entraînant une perte ou un gain de fonction mènent à l’hypercalcémiehypocalciurique familiale de type 1 (HHF1) ou à l’hypocalcémie autosomique dominante (HAD), respectivement

Caractérisation fonctionnelle de sept variations faux-sens dans le gène du récepteur sensible au calcium (CASR)

International audienceLe récepteur sensible au calcium (CaSR) est un RCPG qui régule l’homéostasie du calcium extracellulaire (Ca2+e), codé parle gène CASR. Cette régulation se fait par la mobilisation du calcium intracellulaire (Ca2+i) et la voie de signalisationMAPK. Les mutations du gène CASR entraînant une perte ou un gain de fonction mènent à l’hypercalcémiehypocalciurique familiale de type 1 (HHF1) ou à l’hypocalcémie autosomique dominante (HAD), respectivement