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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.
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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Cells of the Adaptive Immune Response01:23

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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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Special Features of Adaptive Immunity01:20

Special Features of Adaptive Immunity

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The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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Primary Lymphoid Organs01:16

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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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Related Experiment Video

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Murine Model of CD40-activation of B cells
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An Aged/Autoimmune B-cell Program Defines the Early Transformation of Extranodal Lymphomas.

Leandro Venturutti1,2,3, Martin A Rivas4, Benedikt W Pelzer4,5

  • 1Centre for Lymphoid Cancer, BC Cancer, Vancouver, British Columbia, Canada.

Cancer Discovery
|October 20, 2022
PubMed
Summary

Diffuse large B-cell lymphoma (DLBCL) with extranodal spread has poor outcomes. We identified aged/autoimmune memory B cells (AiBC)-like precursors in extranodal DLBCL, suggesting shared pathways and potential for early detection.

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Area of Science:

  • Hematology
  • Immunology
  • Oncology

Background:

  • Extranodal diffuse large B-cell lymphoma (DLBCL) presents with poor prognosis, often linked to the MYD88L265P mutation.
  • The mechanisms of extranodal lymphomagenesis and the role of MYD88L265P in transformation are not fully understood.

Discussion:

  • B cells expressing the MYD88L265P murine equivalent (Myd88L252P) exhibit enhanced activation, proliferation, and differentiation, with a skew towards memory fate.
  • These Myd88L252P-expressing B cells share transcriptional and phenotypic profiles with aged/autoimmune memory B cells (AiBC).
  • AiBC-like cells accumulate in lymphoma-prone animals, and T-BET, a key AiBC regulator, is crucial for the fitness of mutant B cells.

Key Insights:

  • A specific population of prospective lymphoma precursor cells, resembling AiBC, has been identified in extranodal lymphoma contexts.
  • The study reveals overlapping pathogenic trajectories between extranodal lymphomas and autoimmune disorders.
  • T-BET is identified as a critical dependency for these precursor cells, highlighting its role in lymphomagenesis.

Outlook:

  • These findings enable the identification of phenotypically defined precursor cells for early detection of premalignant states.
  • Targeted prophylactic interventions can be developed for high-risk patients based on these precursor cell dependencies.
  • Understanding the spectrum of B-cell disorders, from autoimmunity to lymphoma, opens new avenues for therapeutic strategies.