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Related Concept Videos

Immunodeficiency Diseases01:25

Immunodeficiency Diseases

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Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency...
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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.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
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Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
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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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Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

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An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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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.
Naive T cells that have not yet encountered an antigen express two primary CD...
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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
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IgH sequences in common variable immune deficiency reveal altered B cell development and selection.

Krishna M Roskin1, Noa Simchoni2, Yi Liu3

  • 1Department of Pathology, Stanford University, Stanford, CA 94305, USA.

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|August 28, 2015
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Summary

Common variable immune deficiency (CVID) stems from early B cell abnormalities, impacting antibody production and increasing risks for autoimmunity and lymphoma. These B cell defects occur earlier than previously thought.

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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
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Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
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Area of Science:

  • Immunology
  • Genetics
  • Cell Biology

Background:

  • Common variable immune deficiency (CVID) is a primary immune deficiency characterized by impaired antibody responses, autoimmunity, and increased risk of lymphoid cancers.
  • CVID affects approximately 1 in 25,000 individuals, presenting significant clinical challenges.

Purpose of the Study:

  • To investigate the cellular and molecular basis of CVID by analyzing B cell receptor gene rearrangements.
  • To identify early B cell developmental defects contributing to CVID phenotypes.

Main Methods:

  • High-throughput DNA sequencing of immunoglobulin heavy chain gene rearrangements in 93 CVID patients and 105 controls.
  • Analysis of naïve and memory B cells from a subset of CVID patients and controls.

Main Results:

  • CVID patients exhibit abnormal VDJ rearrangement and complementarity-determining region 3 (CDR3) formation.
  • Decreased selection against long CDR3 antibodies and reduced variable gene replacement were observed in CVID memory repertoires.
  • Evidence suggests B cell divergence from controls as early as the pro-B stage, with abnormal clonal expansion of unmutated B cells.

Conclusions:

  • CVID pathogenesis involves defects in both the diversity of the naïve B cell pool and somatic hypermutation in memory repertoires.
  • These early B cell abnormalities provide potential mechanisms for CVID-associated immunodeficiency, autoimmunity, and lymphoma.