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Related Concept Videos

B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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T Cell Types and Functions01:24

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Regulation of Hematopoietic Stem Cells01:01

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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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T Cell Activation and Clonal Selection01:22

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Flow Cytometric Characterization of Murine B Cell Development
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DNAJA3 regulates B cell development and immune function.

Stephanie L Sayson1, Jia-Ning Fan2, Chien-Liang Ku3

  • 1Department of Life Science, Fu-Jen Catholic University, New Taipei, Taiwan; Institute of Applied Science & Engineering, Fu-Jen Catholic University, New Taipei, Taiwan.

Biomedical Journal
|July 24, 2023
PubMed
Summary
This summary is machine-generated.

The tumor suppressor DNAJA3 (DNAJA3) is vital for B cell development and immune function. Its deficiency impairs B cell maturation, reduces immunoglobulin production, and affects mitochondrial health.

Keywords:
B cell developmentDNAJA3Mitochondria complex proteinsMitochondria dysfunctionTid1

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Area of Science:

  • Immunology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • DnaJ homolog subfamily A member 3 (DNAJA3), also known as tumorous imaginal disc 1 (Tid1), is crucial for T cell development and acts as a tumor suppressor in lymphocyte survival.
  • The specific role of DNAJA3 in B cell development and immune function has not been previously elucidated.
  • This study investigates the function of DNAJA3 in B cells using a B cell-specific DNAJA3 knockout mouse model.

Purpose of the Study:

  • To investigate the physiological function of DNAJA3 in B cell development.
  • To determine the impact of DNAJA3 deficiency on B cell immune function.
  • To elucidate the underlying mechanisms, particularly mitochondrial function, affected by DNAJA3 loss in B cells.

Main Methods:

  • Utilized a B cell-specific DNAJA3 knockout (CD19-Cre/+; DNAJA3flx/flx) mouse model.
  • Characterized B cell populations and mitochondrial content/function via flow cytometry.
  • Assessed B cell blastogenesis (CFSE, MTT assays) and immunoglobulin production (ELISA).
  • Compared DNAJA3 and OXPHOS protein complexes using immunoblotting.

Main Results:

  • DNAJA3 deficiency led to decreased pro-B to immature B cell populations and reduced B220+ cells in bone marrow and immune organs.
  • Significant reductions were observed in B1 (B1b) and B2 B cell subpopulations.
  • B cell blastogenesis activity and immunoglobulin production were diminished in DNAJA3 knockout mice.
  • DNAJA3 deficiency resulted in increased dysfunctional mitochondria, decreased mitochondrial mass, membrane potential, and reduced mitochondrial respiratory complex proteins.

Conclusions:

  • DNAJA3 plays a significant role in B cell development and maturation.
  • DNAJA3 deficiency negatively impacts B cell immune function, including antibody production.
  • Mitochondrial dysfunction is a key mechanism underlying the effects of DNAJA3 loss on B cells.