chapter_7 - Chapter 7 The Development and Survival of...

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Chapter 7 The Development and Survival of Lymphocytes Gene rearrangements Testing whether the rearrangements are productive and the receptor is functional (and replacing nonproductive rearrangements if possible) Testing the specificity of the receptor to provide assurance that it is not anti-self (tolerance) and get rid of cells with anti-self specificity T cells need to be MHC restricted (bind to self MHC) but not anti- self (bind to self molecules). This seems to be somewhat contradictory and introduces a technically difficult problem for T cells Most of this chapter is about the maturation/development of lymphocytes in the absence of foreign antigen (from pre-lymphocyte to mature naïve lymphocyte): Most lymphocyte die before solving all these problems
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Summary of the life of a B cell In the bone marrow, B cell rearrange their Ig genes in the absence of antigen (panel 1). Those B cell with a BCR that bind antigen (self) in the bone marrow die (panel 2). B cell that do not bind antigen in the bone marrow can leave (mature naïve). If they bind antigen in the periphery (and get T help), they are activated (proliferate and differentiate) (panel 3 and 4). Activated B cell become plasma cells or memory cells (panel 4) (Clonal deletion) Plasma cells mostly in bone marrow; memory B cells in lymphoid tissue and circulation Bone marrow Periphery With T help
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Lymphocytes develop from a hematopoietic stem cells Not exactly as shown in chapter 1
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B cell development is dependent on bone marrow stromal cells
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bone marrow periphery Ig gene rearrangements occur in an orderly fashion in developing B cells (every step in this slide is antigen- independent)
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Pre-B cells Immature B cells Bone Marrow Periphery For simplicity, all these stages (before the cell has a functional BCR) as Pre-B cells Mature naïve B cells Nomenclature for this class Pre-B cell : all cells in the B cell lineage before they have a functional BCR Immature B cell : B cell in the bone marrow with a functional BCR and which, upon binding antigen, will be deleted (killed) Mature naïve B cell : B cell in the periphery that have never bound antigen and, upon binding of antigen can be activated (or deleted) (in later chapters, additional names for activated B cell)
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When B cells rearrange their H chain genes they make a pre-B cell receptor using a surrogate light chain to test whether the rearrangement was productive If successful in making a functional H chain, the cell stops rearrangement at the heavy chain locus and divides several times before rearrangements on the light chains Here is why: Case 1 : no division after making a functional H chain. If 20% successful at H and 20% success at L then 4% (20% X 20%) of the cells will be successful (need 100 tries (cells) to get 4 successes).
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chapter_7 - Chapter 7 The Development and Survival of...

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