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Principles of Immunology B Cell Development 3/16/06

Principles of Immunology B Cell Development 3/16/06. “Hard work has a future payoff but laziness pays off now.” Anonymous. Word/Terms List. Class switching Clonal deletion Naïve B cells Stromal cells TD antigens TI antigens. B Cell Development.

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Principles of Immunology B Cell Development 3/16/06

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  1. Principles of ImmunologyB Cell Development3/16/06 “Hard work has a future payoff but laziness pays off now.” Anonymous

  2. Word/Terms List • Class switching • Clonal deletion • Naïve B cells • Stromal cells • TD antigens • TI antigens

  3. B Cell Development Maturation-Stem cells to mature, naïve B cells Activation-Ag binding; initiation of cell changes Differentiation-Cell division and changes into effector B cells (plasma cells) and memory B cells

  4. Lymphopoiesis • Occurs in yolk sac, fetal liver then bone marrow throughout rest of life • Mature, naïve B cells released into circulation • B cell production occurs throughout life; does not wane as does T cell production • About 5 million produced per day • Only 10% of B cells mature • Naïve B cells survive about one week • Undergo negative selection

  5. B Cell Maturation • Hematopoietic stem cells(HSC) • Lymphoid stem cell (progenitor) • B cell progenitor (pro-B cell) • Pre-B cell • Immature B cell • Mature, naïve B cell

  6. B Cell Changes • Pro B cells • Rearrangement of Ig heavy chaingenes (D to J joining followed by V to DJ) • Not all rearrangements result in complete mu variable region sequences • Expression of CD45R and CD19 • Further maturation is dependent on direct interaction with BM stromal cells • c-Kit on pro B is activated by SCF on stromal cells

  7. B Cell Changes • Pre B cells • Cell division occurs • Rearrangement of Ig light chaingenes (V to J joining) • Expression of IL7 receptor • Expression of mu heavy chains in association with Ig alpha-Ig beta heterodimer • Pre B cell receptor uses surrogate light chains • Shuts down further Ig gene rearrangement

  8. B Cell Changes • Immature B cells • IgM expressed on surface • B cell receptor appears • Cells interact with self Ags • Negative selection (clonal deletion) occurs

  9. B Cell Changes • Mature B cells • Migrate out of bone marrow • Both IgM and IgD expressed on surface • Cell division occurs • Rearrangement of Ig light chaingenes (V to J joining) • Expression of IL7 receptor • Expression of mu heavy chains in association with Ig alpha-Ig beta heterodimer • Pre B cell receptor uses surrogate light chains • Shuts down further Ig gene rearrangement

  10. B Cell Activation • Triggered by combining with Ag • Two types of Ags that activate B cells • Thymus dependent Ag e.g. soluble proteins • Thymus independent Ag • Type 1, e.g. LPS • Type 2, e.g. capsular polysaccharides • The reaction to thymus independent antigens is not as strong, memory cells are not produced and class switching does not occur

  11. B Cell Activation • Activation signals • Two signals required • In TI Ags both signals occur post antigen binding without T helper cells • In TD Ags, Ag binding provides one signal and CD40/CD40L ligand on T helper cell provides the second

  12. B Cell Activation • Signaling pathways • Similar to T cell signaling • Protein tyrosine kinase (Src) • Phosphorylated tyrosines on ITAMS dock the Syk kinase • Ultimate effects are on gene expression • Co receptor • Three protein complex • Provides signals that modify B cell

  13. B Cell/T Cell Interaction • B cells as Ag binding and Ag presenting cells • B cells are able to react to lower concentrations of Ag • Co-stimulation with CD40/CD40L • Role of interleukins (IL2,4,5)

  14. B Cell Subsets • B1 • CD5 marker • More responsive to CHO Ags • Seen in peritoneum • B2 • Most B cells (95%) • Drive the Ag response in secondary lymphoid organs

  15. Humoral Response • Effector cells and memory cells • Naïve B cells vs. memory cells, primary vs. secondary response

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