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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 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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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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Primary Lymphoid Organs01:16

Primary Lymphoid Organs

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Primary lymphoid organs are pivotal in the formation, development, and maturation of lymphocytes, the white blood cells that serve as the backbone of our immune system. This crucial function underscores their fundamental role in maintaining our overall health and immunity. The two primary lymphoid organs of prime importance are the red bone marrow and the thymus.
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Secondary organs, including lymph nodes, the spleen, and mucosa-associated lymphoid tissue (MALT), work harmoniously to protect us from disease and infection.
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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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Clonal evolution in diffuse large B-cell lymphoma with central nervous system recurrence.

T Magnes1, S Wagner1, A R Thorner2

  • 1Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.

ESMO Open
|January 5, 2021
PubMed
Summary
This summary is machine-generated.

Genetic analysis of secondary central nervous system lymphoma (SCNSL) reveals significant mutations in key genes like MYC, suggesting clonal evolution contributes to treatment resistance in diffuse large B-cell lymphoma (DLBCL) patients.

Keywords:
clonal evolutiondiffuse large B-cell lymphomamassively parallel sequencingsecondary central nervous system lymphoma

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Secondary central nervous system lymphoma (SCNSL) has a poor prognosis.
  • Genetic landscape of SCNSL remains poorly understood compared to primary diffuse large B-cell lymphoma (DLBCL).

Purpose of the Study:

  • To compare the genetic profiles of primary DLBCL biopsies with matched CNS recurrences.
  • To investigate the genetic basis and clonal evolution of SCNSL.

Main Methods:

  • Targeted sequencing of 216 DLBCL-associated genes in paired lymph node and CNS samples from six patients.
  • Comparison of mutation profiles to identify genetic differences and clonal evolution.

Main Results:

  • Sequencing successful in five patients; all showed discordant mutations.
  • Four patients had mutations exclusive to the CNS recurrence.
  • Discordant mutations identified in key lymphoma genes (MYC, CARD11, EP300, CCND3); two patients showed substantial genetic divergence.

Conclusions:

  • Provides insight into the genetic landscape of SCNSL.
  • Substantial clonal diversification at relapse may be a mechanism for treatment resistance in DLBCL.