The Experts below are selected from a list of 57 Experts worldwide ranked by ideXlab platform

Michael Karin - One of the best experts on this subject based on the ideXlab platform.

  • kinase mekk1 is required for cd40 Dependent activation of the kinases jnk and p38 germinal center formation b cell proliferation and antibody production
    Nature Immunology, 2007
    Co-Authors: Ewen Gallagher, Thomas Enzler, Atsushi Matsuzawa, Amy Anzelonmills, Dennis C Otero, Ryan G Holzer, Edith M Janssen, Min Gao, Michael Karin
    Abstract:

    Mice lacking activity of the kinase MEKK1 ('Map3k1(deltaKD)' mice) have defective activation of the kinase Jnk and increased production of T helper type 2 cytokines after T cell receptor ligation. Here we show that Map3k1(deltaKD) mice had defective germinal center formation and diminished production of antibodies recognizing Thymus-Dependent Antigens. Those defects were B cell intrinsic, as MEKK1 was necessary for CD40-mediated activation of the kinases Jnk and p38 and transcription factor c-Jun, as well as for expression of cyclin D2 and activation-induced deaminase. MEKK1 was recruited to CD40 and adaptor molecule TRAF2 after CD40 ligation, and Map3k1(deltaKD) B cells were hypoproliferative after CD40 stimulation. Our data emphasize that MEKK1 is an essential component of signaling cascades needed for Thymus-Dependent Antigen-induced B cell proliferation and antibody production.

Elena Vigorito - One of the best experts on this subject based on the ideXlab platform.

  • a crucial role for the p110δ subunit of phosphatidylinositol 3 kinase in b cell development and activation
    Journal of Experimental Medicine, 2002
    Co-Authors: Elizabeth Clayton, Giuseppe Bardi, Sarah Bell, David Chantry, Peter C Downes, Alexander Gray, Lisa A Humphries, David J Rawlings, Helen Reynolds, Elena Vigorito
    Abstract:

    Mice lacking the p110δ catalytic subunit of phosphatidylinositol 3-kinase have reduced numbers of B1 and marginal zone B cells, reduced levels of serum immunoglobulins, respond poorly to immunization with type II Thymus-inDependent Antigen, and are defective in their primary and secondary responses to Thymus-Dependent Antigen. p110δ−/− B cells proliferate poorly in response to B cell receptor (BCR) or CD40 signals in vitro, fail to activate protein kinase B, and are prone to apoptosis. p110δ function is required for BCR-mediated calcium flux, activation of phosphlipaseCγ2, and Bruton's tyrosine kinase. Thus, p110δ plays a critical role in B cell homeostasis and function.

Ewen Gallagher - One of the best experts on this subject based on the ideXlab platform.

  • kinase mekk1 is required for cd40 Dependent activation of the kinases jnk and p38 germinal center formation b cell proliferation and antibody production
    Nature Immunology, 2007
    Co-Authors: Ewen Gallagher, Thomas Enzler, Atsushi Matsuzawa, Amy Anzelonmills, Dennis C Otero, Ryan G Holzer, Edith M Janssen, Min Gao, Michael Karin
    Abstract:

    Mice lacking activity of the kinase MEKK1 ('Map3k1(deltaKD)' mice) have defective activation of the kinase Jnk and increased production of T helper type 2 cytokines after T cell receptor ligation. Here we show that Map3k1(deltaKD) mice had defective germinal center formation and diminished production of antibodies recognizing Thymus-Dependent Antigens. Those defects were B cell intrinsic, as MEKK1 was necessary for CD40-mediated activation of the kinases Jnk and p38 and transcription factor c-Jun, as well as for expression of cyclin D2 and activation-induced deaminase. MEKK1 was recruited to CD40 and adaptor molecule TRAF2 after CD40 ligation, and Map3k1(deltaKD) B cells were hypoproliferative after CD40 stimulation. Our data emphasize that MEKK1 is an essential component of signaling cascades needed for Thymus-Dependent Antigen-induced B cell proliferation and antibody production.

Elizabeth Clayton - One of the best experts on this subject based on the ideXlab platform.

  • a crucial role for the p110δ subunit of phosphatidylinositol 3 kinase in b cell development and activation
    Journal of Experimental Medicine, 2002
    Co-Authors: Elizabeth Clayton, Giuseppe Bardi, Sarah Bell, David Chantry, Peter C Downes, Alexander Gray, Lisa A Humphries, David J Rawlings, Helen Reynolds, Elena Vigorito
    Abstract:

    Mice lacking the p110δ catalytic subunit of phosphatidylinositol 3-kinase have reduced numbers of B1 and marginal zone B cells, reduced levels of serum immunoglobulins, respond poorly to immunization with type II Thymus-inDependent Antigen, and are defective in their primary and secondary responses to Thymus-Dependent Antigen. p110δ−/− B cells proliferate poorly in response to B cell receptor (BCR) or CD40 signals in vitro, fail to activate protein kinase B, and are prone to apoptosis. p110δ function is required for BCR-mediated calcium flux, activation of phosphlipaseCγ2, and Bruton's tyrosine kinase. Thus, p110δ plays a critical role in B cell homeostasis and function.

Carrie N Arnold - One of the best experts on this subject based on the ideXlab platform.

  • the germinal center response is impaired in the absence of t cell expressed cxcr5
    European Journal of Immunology, 2007
    Co-Authors: Carrie N Arnold, Daniel J Campbell, Martin Lipp, Eugene C Butcher
    Abstract:

    Germinal centers support the differentiation of memory B cells and long-lived antibody-secreting cells during infection or upon vaccination. Here, we constructed mice with T cells that selectively lack the chemokine receptor CXCR5 to determine if expression of this receptor by T cells is mandatory for germinal center formation and function. In these animals, germinal centers that are properly localized in B cell follicles and contain T cells do form after immunization with a Thymus-Dependent Antigen. However, fewer and smaller germinal centers form, resulting in a significant reduction in the frequency of germinal center B cells. The defect in germinal center formation is paralleled by decreased frequencies of isotype-switched antibody-secreting cells in the spleen and bone marrow and reduced serum concentrations of total and high-affinity hapten-specific IgG(1). The results demonstrate that although CXCR5-Dependent T cell positioning is important for maximal induction and expansion of germinal centers, stimulation of isotype class switching, and development of antibody-secreting cells that seed the spleen and bone marrow, it is not absolutely required for the formation and function of follicular germinal centers.