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"Production of new lymphocytes (..."
  • Production of new lymphocytes (lymphopoiesis): in central lymphoid tissues
  • B cells: bone marrow; fetus (fetal liver, yolk sac)
  • T cells: precursor cells in bone marrow and then migrate to thymus


  • Ag specificity of an individual lymphocyte is determined early in its differentiation by gene rearrangement. The early stages of B and T cell development proceed along broadly similar lines.
  • Specificity and affinity of the receptors determine the fate of the immature lymphocytes


  • -Positive selection: interact weakly with self Ag. Receive signals to survive. Eg. α:β T cells recognize peptide bound to MHC
  • -Negative selection: lymphocytes whose receptors bind strongly or not at all to self antigen and receive signals to die (immunological tolerance).


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B cell life history
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T cell life history
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"The stages of B cell..."
  • The stages of B cell development and VDJ recombination
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Ig Rearrangements and Cell Surface Markers
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T cells also originate in bone marrow but develop in the thymus
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The thymus is critical for the T cell maturation
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The stages of T cell development are marked by changes in cell-surface molecules
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α:ß pathway
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Thymocytes at different stages are found in distinct parts of thymus
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Successive rearrangement of the immunoglobulin light-chain variable segments can increase probability for cell-surface expression of the B cell receptor
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Figure 7-19 part 1 of 2
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Figure 7-19 part 2 of 2
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Immunodeficiency can occur through abberant signaling of the pre-B receptor
  • Btk: Bruton’s tyrosine kinase. Mutation causes a profound B-lineage specific immune deficiency (Bruton’s X-linked agammaglobulinemia, XLA) in which no mature B-cells are produced.
  • Mouse equivalent (xid) more “leaky”; some mature B cells get by pre-B block, but they are signaling compromised as well.
  • Tec family tryrosine kinase regulated via PKC, Ca2+ pathway (Chapter 6);
  • Mutations in plextrin homology domain (PHD)
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Figure 7-19 part 2 of 2
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"Gene rearrangement"
  • Gene rearrangement: Comparison in B cell and T cell
  • SIMILARITIES
  • T cells have almost identical strategies as B cells
  • Use the same enzymes
  • Light chain ↔ TCRα(V, J) ; Heavy chain ↔ TCRß (V, D, J)
  • One productively rearranged VDJ is expressed with surrogate chain(s) as soon as it is made
  • The mature receptor is required for further development and shutting down further rearrangement


  • DIFFERENCES
  • Three separate lineages of T cells: α:ß, γ:δ, and α:ß-NK
  • Non productive ß-chain VDJ can be rescued by subsequent rearrangement because of two clusters of Dß and Jß upstream of two Cß
  • The chances are higher for productive rearrangement of ß chain that for Ig heavy chain.
  • B cells: Final assembly of an immunoglobulin leads to the cessation of gene rearrangement and initiates further differentiation
  • T cells: rearrangement of V α continues until positive selection by self-peptide: self-MHC complex
  • RAGs are transcriptionally regulated by different enhancers and V segments loci are differentially accessible at chromatin level.
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"Pre-T cell receptor (pT..."








  • Pre-T cell receptor (pTα:ß) , analogous to pre-B cell receptor (µ:VpreB:λ5), forms a complex with CD3
  • triggers the phosphorylation and degradation of RAG2è Halting ß chain rearrangement and ensure allelic exclusion
  • Induces cell proliferation and the expression of co-receptors, CD4 and CD8
  • This event is dependent on Lck


  • First α chain rearrangement delete δ genes
  • Productive α chain is paired with ß chain è DP CD3low selection for its ability to recognize self peptides with self MHC
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