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Announcements. Case Studies: Case 10, 11, & 12 provided.. Please do case study 10 & 12 only. Case 11 was provided for information that may assist with Case 12. Due Feb 15, 2008 Exam 2: Wed Feb 20, 2008. Ch. 2 & 4. Class Switching occurs as the B cells are stimulated by Ag.

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Announcements

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  1. Announcements • Case Studies: • Case 10, 11, & 12 provided.. Please do case study 10 & 12 only. Case 11 was provided for information that may assist with Case 12. • Due Feb 15, 2008 • Exam 2: • Wed Feb 20, 2008. • Ch. 2 & 4

  2. Class Switching occurs as the B cells are stimulated by Ag. Differentiation into Plasma Cells.

  3. Can rearrangement be nonproductive? • If we have a switch from mu to alpha1, can we have revert back to the mu?

  4. Mechanism for class switching not completely understood! • AID, UNG, & APE1 participate by making single strand nicks in DNA.

  5. B cell Development Chapter 4

  6. Foreign Antigen Independent Foreign Ag Dependent

  7. Late Pro-B cell

  8. Surrogate Light Chains in the Large Pre-B cells:

  9. Proliferates to produce 32-64 progeny Late Pro-B cell Naïve B cell

  10. B cell Development is dependent upon: • Stromal Cells: • Make specific cell surface contacts with developing B cells. • Adhesion molecules & ligands. • Secrete cytokines & growth factors. • Productive Rearrangement of the L & H chain gene segments.

  11. Stromal Cell Interaction with Developing B cells.

  12. Cell to Cell contact is mediated by CAMs- Cell Adhesion Molecules: • VLA-4: on stem cells. • Binds VCAM-1 on stromal cells • Kit: binds to SCF & has tyrosine kinase activity. • Signals proliferation • Up-regulation of IL7R • Stem Cell Factor (SCF)- membrane bound cytokine on stromal cells.

  13. Kit functions as a tyrosine kinase & mediates signal transduction IL-7 downregulates expression of kit & induces development.

  14. Endosteum- inner bone surface Pro B cells detected- TdT Center of BM

  15. B cell development is dependant upon Productive Rearrangement of the L & H gene segments: 1/2 successful ~ ½ nonproductive

  16. Light chain Rescue: • The L chain gene region can have more than 1 attempt at a single locus.

  17. Only 1 H chain allele & 1 L chain allele is expressed! • G.D. Yancopoulis & R.W. Alt- Model for allelic exclusion: • Once a productive rearrangement is obtained, its encoded protein is expressed & this proteins presence acts as a signal to prevent further gene rearrangement.

  18. Primary check point. • Is RAG being produced in the late pre B cell?

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