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Project summary The cellular and molecular events underlying the generation of self-reactive antibodies in autoimmunity remain poorly understood. Notably, marginal zone (MZ) B cells are enriched for self-reactive B cells, and are known to generate antibody-secreting plasma cells exceptionally quickly compared to other B cells. This R21 project centers on understanding the molecular mechanisms through which MZ B cells generate plasma cells with accelerated kinetics, with a focus on defining extracellular cues and associated intracellular signaling pathways that prime MZ B cells for differentiation. The central hypothesis guiding this work is that the mTOR/mTORC1 kinase, an emerging biomarker in lupus and related autoimmune diseases, couples BAFF-receptor signaling and expression of relevant plasma cell genes to facilitate rapid induction of antibody synthesis. To test this hypothesis we will: 1) Define the role of mTOR/mTORC1 signaling in plasma cell priming, and 2) Explore the identity of extracellular inputs driving plasma cell priming in situ. These studies will enhance knowledge of the processes underlying the generation of all plasma cells including those secreting pathogenic self-reactive antibodies.
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Biochemical Mechanisms for Sustained Humoral Immunity
  • 批准号:
    10637251
  • 项目类别:
  • 资助金额:
    $64.81万
  • 财政年份:
    2023
  • 负责人:
    David M Allman
  • 依托单位:
The Notch Pathway in Antigen Design
  • 批准号:
    10575892
  • 项目类别:
  • 资助金额:
    $26.4万
  • 财政年份:
    2023
  • 负责人:
    David M Allman
  • 依托单位:
Plasma Cell Regulation by Purinergic Receptors
  • 批准号:
    10441466
  • 项目类别:
  • 资助金额:
    $20.31万
  • 财政年份:
    2021
  • 负责人:
    David M Allman
  • 依托单位:
Plasma Cell Regulation by Purinergic Receptors
  • 批准号:
    10240081
  • 项目类别:
  • 资助金额:
    $24.38万
  • 财政年份:
    2021
  • 负责人:
    David M Allman
  • 依托单位:
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