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Lymphocyte Development Overview: B and T Cell Development Stages

Learn about the intricate stages of B and T cell development, from gene rearrangements to receptor specificities. Understand the processes of negative and positive selection for immunological tolerance and MHC restriction. Explore the role of central and secondary lymphoid tissues in lymphocyte maturation. Discover the cellular interactions and signals crucial for lymphocyte development in both bone marrow and thymus.

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Lymphocyte Development Overview: B and T Cell Development Stages

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  1. Topics • Overview • B cell development • T cell development BIOS 486A / 586A

  2. Lymphocyte development overview • Ag receptors in B and T cells are immensely variable • Diversity is generated during development by gene rearrangement • Lymphopoiesis occurs mainly in Central Lymphoid Tissues (Bone Marrow & Thymus) BIOS 486A / 586A

  3. Lymphocyte development overview (Cont) • Receptor diversity is produced by gene rearrangement and is random • Includes specificities that will bind to SELF • Lymphocytes go through a process of selection • Self-recognizing cells are removed from the system during development (Negative selection) • Sells that recognize self antigens weakly or that recognize self antigens in a particular way receive a survival signal (positive Selection) BIOS 486A / 586A

  4. Lymphocyte development overview (Cont) • Negative Selection ensures Immunological Tolerance • Positive Selection ensures MCH Restriction (T-cells) • Default fate = cell death • Most lymphocytes generated in the Bone Marrow do not survive • In the fetus lymphocytes are generated in the liver BIOS 486A / 586A

  5. In the fetus and juvenile individuals: • large production of new lymphocytes that populate the peripheral lymphoid tissues • In the mature individual: • New T cell production slows down. T cells are maintained by division of mature T cells. • New B cells are constantly being produced BIOS 486A / 586A

  6. BIOS 486A / 586A

  7. 4 stages of B cell development BIOS 486A / 586A Fig 6.1

  8. Development requires signals from to microenvironment to start gene rearrangements • Stromal cells (Stroma = mattress) • Specific adhesion contacts via interaction of cell-adhesion molecules and their ligands • Provide growth factors that stimulate lymphocyte differentiation and proliferation BIOS 486A / 586A

  9. B cell early development in the Bone Marrow BIOS 486A / 586A

  10. Development occurs in stages • is measured by successful rearrangement of genes and expression of receptor molecules • Development is accompanied by expression of other cell surface and intracellular proteins BIOS 486A / 586A

  11. BIOS 486A / 586A

  12. Productive rearrangement leads to protein expression • Non-productive rearrangement leas to apoptosis BIOS 486A / 586A

  13. B cell development in Secondary lymphoid organs • Immature cells complete development in secondary lymphoid organs • Spleen, Lymph nodes, MALT • Small proportion complete maturation and survive to recirculate between Lymphoid organs and the blood • Survival is a consequence of competition for a place in the pool of long-lived recirculating B cells • Follicular dendritic cells, located in FOLLICLES provide survival signals to all cells • B cells stay for one day in follicle BIOS 486A / 586A

  14. Immature B cells (Bone Marrow) Binding to Ag presented by cells? (multivalent) NO YES Apoptosis Binding to soluble Ag? NO YES Anergy Enter the secondary lymphoid tissue? YES NO Short life Mature B cells (Secondary Lymphoid tissues) B cell selection BIOS 486A / 586A

  15. T cell Development BIOS 486A / 586A

  16. T cell origin Fetus : Bone Marrow & Liver Infants, juveniles: Bone Marrow & Thymus – High production Adults: Thymus atrophied – #s maintained by division of Mature T cells BIOS 486A / 586A

  17. Thymic stroma BIOS 486A / 586A

  18. BIOS 486A / 586A

  19. B cell precursor T cell precursor B cell : : Th 1 Th 2 CD4 T helper cells CD8 Cytotoxic T cells Lymphid precursor BIOS 486A / 586A

  20. Progenitor cells enter thymus Differentiate into • Dendritic cells • : • : Double negative cells CD3- CD4- CD8- • chain gene rearrangement Double positive cells CD3+ CD4+ CD8+  chain gene rearrangement Single positive cells CD3+ Either CD4+ orCD8+ T cell development Fig 7.3 Cortex Medulla 7.8 BIOS 486A / 586A

  21. MHC restriction (a) (a) T cell (a) Y X X MHCa MHCb MHCa (a) Antigen presenting cell (b) (a) Fig 5.16 BIOS 486A / 586A

  22. Co-stimulation / Adhesion Molecules BIOS 486A / 586A

  23. CD3+ CD4 +CD8+ CD3+ CD4 +CD8+ CD3+ CD4 +CD8+ CD3+ CD4 +CD8+ CD3+ CD4 +CD8+ Thymic APC YES NO Rescue Ensures MHC restriction Death in 3 or 4 days Positive Selection of T cells Good interaction between TCR – MHC? BIOS 486A / 586A

  24. CD3+ CD4 +CD8+ Thymic APC Very strong interaction between TCR – MHC? YES NO CD3+ CD4 + CD3+ CD4 + CD3+ CD4 + CD3+ CD4 + CD3+ CD8+ CD3+ CD8+ CD3+ CD8+ CD3+ CD8+ Apoptosis Negative Selection of T cells BIOS 486A / 586A

  25. BIOS 486A / 586A Fig 7.23 4th Ed

  26. T cells monitor APC If interaction, T cells proliferate and differentiate If no interaction, T cells leave Cell – Cell interactions in the Lymph Node T cells enter lymph node Fig 8.2 BIOS 486A / 586A

  27. BIOS 486A / 586A

  28. BIOS 486A / 586A

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