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    Lymphocyte Development

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    Agourram Taieb
    Lymphocytes develop through distinct stages: 1. B and T cells develop antigen receptors through gene rearrangement before passing selection checkpoints to eliminate self-reactive cells. 2. Cells that pass selection are activated by antigen exposure and differentiate into effector and memory lymphocytes. 3. Defects in any stage of development can disrupt lymphocyte maturation and increase cancer risk. Precise cytokine signals and cell-cell interactions are required to guide each transition.

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    Lymphocyte Development

    Uploaded by

    Agourram Taieb
    493 views48 pages
    Lymphocytes develop through distinct stages: 1. B and T cells develop antigen receptors through gene rearrangement before passing selection checkpoints to eliminate self-reactive cells. 2. Cells that pass selection are activated by antigen exposure and differentiate into effector and memory lymphocytes. 3. Defects in any stage of development can disrupt lymphocyte maturation and increase cancer risk. Precise cytokine signals and cell-cell interactions are required to guide each transition.

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    Lymphocytes develop through distinct stages: 1. B and T cells develop antigen receptors through gene rearrangement before passing selection checkpoints to eliminate self-reactive cells. 2. Cells that pass selection are activated by antigen exposure and differentiate into effector and memory lymphocytes. 3. Defects in any stage of development can disrupt lymphocyte maturation and increase cancer risk. Precise cytokine signals and cell-cell interactions are required to guide each transition.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    493 views48 pages

    Lymphocyte Development

    Uploaded by

    Agourram Taieb
    Lymphocytes develop through distinct stages: 1. B and T cells develop antigen receptors through gene rearrangement before passing selection checkpoints to eliminate self-reactive cells. 2. Cells that pass selection are activated by antigen exposure and differentiate into effector and memory lymphocytes. 3. Defects in any stage of development can disrupt lymphocyte maturation and increase cancer risk. Precise cytokine signals and cell-cell interactions are required to guide each transition.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    of 48

    Lymphocyte development

    and survival

    Chapter 7
    Objectives
    • Describe or construct flow charts showing the
    stages in development of B cells and T cells,
    including:
    – The general characteristics (surface
    markers, etc) of lymphocytes at each stage
    – Other types of cells or cytokines that are
    required at each stage
    – What happens to cells which fail to complete
    a stage of development
    • Predict how specific genetic defects would
    alter lymphocyte development
    Hematopoiesis

    •Lymphopoiesis mainly occurs in


    central lymphoid tissues
    Major stages of development in
    lymphocytes
    Expression of antigen receptor

    Testing for appropriate


    antigen recognition properties
    (tolerance to self)

    Activation by antigen

    Differentiation
    Overview of B cell development
    Overview of T cell development
    B cell development
    Expression of antigen receptor
    (immunoglobulin)
    B cell development: Expression of Ig

    • Stromal cells in the bone marrow provide cytokines and


    support required for early B cell development
    – Interleukin-7 (IL-7)
    – Cell adhesion molecules (CAMs)
    B cell development: Expression of Ig
    B cell development: Expression of Ig
    B cell development: Expression of Ig
    B cell development: Expression of Ig

    RAG
    B cell development: Expression of Ig
    •Rescue of B cells with nonproductive rearrangments
    B cell development

    Expression of antigen receptor

    Testing for appropriate


    antigen recognition properties
    (tolerance to self)

    • Negative selection: selection of cells that do NOT


    bind to self antigens
    B cell development: Negative selection
    B cell development: Negative selection
    • Self-reactive B
    cells may undergo
    further light
    chain
    rearrangement
    B cell development: Negative selection

    • Some self antigens are only expressed in the


    periphery

    • High levels of cross-linking antigen in periphery


    can induce B cell anergy
    B cell development

    Expression of antigen receptor

    Testing for appropriate


    antigen recognition properties
    (tolerance to self)

    Activation by antigen
    B cell development: activation by
    antigen
    B cell development: activation by
    antigen
    • Chemokines attract and retain B cells in the lymph nodes
    –CXCL13
    B cell development: activation by
    antigen
    B cell development

    Expression of antigen receptor

    Testing for appropriate


    antigen recognition properties
    (tolerance to self)

    Activation by antigen

    Differentiation
    B cell development: differentiation

    • Activated B cells undergo clonal expansion

    • Progeny differentiate into plasma cells or


    memory B cells
    – Isotype switching and somatic
    hypermutation occur
    B cell cancers
    • B cell tumors arise
    from cells at various
    stages of
    development

    • Retain characteristics
    of the normal B cell
    equivalent
    Overview of T cell development
    Some lymphoid progenitors migrate
    to the thymus
    The importance of the thymus for T
    cell development
    T cell development

    Expression of antigen receptor

    Testing for appropriate


    antigen recognition properties
    (tolerance to self)

    Activation by antigen

    Differentiation
    T cell development

    Expression of TCR
    T cell development: expression of TCR

    • Progenitors arriving from


    the bone marrow do not
    express TCR, CD3, CD4, or
    CD8

    • Successful rearrangement of
    TCR β chain results in
    expression of a pre-T-cell
    receptor, CD3, CD4, and CD8
    T cell development: expression of TCR
    T cell development: expression of TCR
    T cell development: expression of TCR
    T cell development

    Expression of TCR

    Testing for appropriate


    antigen recognition properties
    (tolerance to self)
    T cell development: selection for
    self-tolerance
    • Selection for self-tolerance in T cells
    requires two stages:

    – Positive selection for ability to bind to


    MHC : peptide complexes

    – Negative selection eliminates T cells with


    high-affinity binding to MHC : self peptide
    complexes
    T cell development: Positive selection
    T cell development: Positive selection
    T cell development: Negative selection
    The role of thymic cells in positive
    and negative selection
    Mechanisms of positive and negative
    selection
    •Mechanisms that
    differentiate positive
    and negative selection
    are not clear
    – Difference in
    affinity?
    – Other signals
    required?
    T cell development

    Expression of TCR

    Testing for appropriate


    antigen recognition properties
    (tolerance to self)

    Activation by antigen
    T cell development: activation by
    antigen
    T cell development: activation by
    antigen
    • As with B cells, self-reactive T cells can also be
    eliminated in the periphery
    –Activation-induced cell death
    –Anergy
    T cell development

    Expression of TCR

    Testing for appropriate


    antigen recognition properties
    (tolerance to self)

    Activation by antigen

    Differentiation
    T cell development: differentiation

    • Activated T cells undergo clonal expansion

    • Differentiation of progeny into effector or


    memory cells
    – Cytotoxic T lymphocytes
    – Helper T cells (Th1, Th2)
    – Memory T cells
    T cell cancers

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