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Related Concept Videos

B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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...
T Cell Types and Functions01:24

T Cell Types and Functions

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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Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

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Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation
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Effective collaboration between IL-4 and IL-21 on B cell activation.

Toru Saito1, Daisuke Kitayama, Akemi Sakamoto

  • 1Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan.

Immunobiology
|July 29, 2008
PubMed
Summary

Interleukin-21 (IL-21) enhances B cell proliferation and differentiation when sequentially applied after Interleukin-4 (IL-4). This specific order is crucial for synergistic effects in B cell activation and antibody class switching.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Interleukin-4 (IL-4) and Interleukin-21 (IL-21) are known to synergistically promote B cell activation.
  • The precise collaborative roles and optimal sequential stimulation order of IL-4 and IL-21 in B cell responses remain unclear.

Purpose of the Study:

  • To investigate the synergistic effects of sequential stimulation with IL-4 and IL-21 on B cell proliferation, class switching, and plasma cell differentiation.
  • To determine the optimal order and timing for IL-4 and IL-21 co-stimulation to achieve maximal B cell responses.

Main Methods:

  • Splenic B cells were sequentially stimulated with anti-IgM antibody and anti-CD40 antibody plus IL-4, followed by IL-21, or vice versa, at different time intervals.
  • Cell proliferation, IgG1 class switching frequency, plasma cell differentiation, and the expression of Activation-Induced Cytidine Deaminase (AID) and Blimp1 mRNA were quantified.
  • CXCR4(-) and CXCR4(+) B cell populations were analyzed following specific stimulation protocols.

Main Results:

  • Sequential stimulation with IL-4 followed by IL-21 (2-day interval) continuously enhanced B cell proliferation, IgG1 class switching, and plasma cell differentiation up to day 5.
  • This IL-4 then IL-21 sequence significantly increased AID and Blimp1 mRNA levels compared to IL-4 alone.
  • Reversing the order (IL-21 then IL-4) or using intervals longer than 1 day abolished the synergistic effect.
  • Early low-dose IL-4 followed by IL-21 or IL-4 on day 2 differentially induced proliferation and differentiation of CXCR4(-) and CXCR4(+) B cells, respectively.

Conclusions:

  • The order of cytokine application is critical for achieving synergistic effects between IL-4 and IL-21 in B cell activation.
  • IL-21 effectively potentiates the proliferation and differentiation of B cells pre-activated with IL-4, particularly the CXCR4(-) subset.
  • Optimal sequential stimulation involves IL-4 followed by IL-21 within a specific timeframe to maximize B cell responses and antibody production.