Lectures 4 - Lymphocyte development Flashcards
> What transcription factor tells haematopoetic stem cell to become a B cell?
If this factor is not expressed, what happens to the lymphocyte?
> PAX5
> If cells don’t express PAX5 they won’t become a B cell, and they will leave bone marrow and migrate to thymus.
What are two examples of markers which are expressed on B cells which show they are B cells ?
CD45 then CD19
Describe the process of B cell development.
- The Heavy chain is rearranged first and then moves to cell surface with Iga and Igb ( invariant protein which all B cells have) and the surrogate light chain. This is the pre-BCR.
- If the heavy chain is seen to be functional, RAG1 and RAG2 (needed for gene rearrangement) are turned off. 5-6 rounds of cell division occurs and the surrogate light chain expression stops.
- Then RAG1/2 are turned on again to start light chain rearrangement on the pre-BCR. Kappa light chain is rearranged first, then lambda if kappa didn’t work.
How many chances of rearrangements do light chains have?
For kappa and lamda light chains there are two chromosomes for both. For each chromosome, there are up to 5 J genes, so 5 chances for rearrangement on each chromosome. Therefore there are up to 10 chances for each light chain.
What happens to B cells if they bind multivalent self antigens?
- CLONAL DELETION - causes them to die by apoptosis
- RECEPTOR EDITING - further rearrangement of light chain to try and chain the B cell to make it not bind to self antigens
What happens if B cells bind to soluble self antigens? (this means ones which are floating, not attached to a cell surface)
They migrate to periphery and become unresponsive (anergic).
When do B cells become activated?
What can activated B cells in the periphery develop into?
- They become activated when they bind to foreign antigen.
- Plasma cells and memory cells.
What are the T cell progenitor cells called in the thymus?
thymocytes
Describe the development of T cells.
- T cell precursors are produced in the bone marrow then migrate to thymus, where they are called thymocytes.
- Thymocyte commits to T cell lineage (either a/b or gamma/delta) by NOTCH signalling.
- Rearrangement of TCR genes - beta first (remember beta gene is similar to heavy Ig gene in B cells). A pre-T cell receptor is also expressed here. Then TCR-a genes are rearranged.
- once rearranged, the T cell acquires markers - CD3, CD4 and CD8. Only TCR a/b acquire CD4 and CD8.
- Now you are left with mature T cells in the thymus, expressing both CD4 AND CD8.
- Whilst still in the thymus, T cells undergo positive and negative selection.
- If T cells survive thymic selection, they exit the thymus into the peripheral lymphoid organs as CD8+ T cells that recognise Ag on MHC 1, or CD4+ T cells that recognise MHC class 2.
What is positive selection of T cells and where does it occur?
Positive selection occurs on cortical epithelial cells in thymus - (CORTEX).
Positive selection is selecting the cells which recognise self MHC and self peptides. These cells then move to medulla, where negative selection occurs.
What is negative selection of T cells and where does it occur?
Negative selection is removing the cells which have too high an affinity for self MHC and self peptides on thymic dendritic cells and macrophages, to stop autoimmunity. They are removed by clonal deletion.
Occurs in medulla of thymus.
Where is the thymus located?
Anterior mediastinum
What is the CD3 complex - T cells?
CD3 complexes are on all T cells. CD3 sends signal to T cell nucleus when TCR comes into contact with MHC.
Gamma/delta T cells are less common and do not express CD4 or CD8. Where are the majority of these T cells found?
epithelial tissues at mucosal surfaces
