B cell Development Flashcards
Where do B cells develop?
Hematopoietic stem cells in the bone marrow, which express the PAX5 transcription factor
How many B cells are produced daily?
~3 × 10¹⁰ B cells per day.
What processes are involved in B cell development?
- Rearrangement and expression of immunoglobulin (Ig) genes.
- Expression of lymphocyte and B-cell specific markers (e.g. CD45, then CD19)
- Removal of self-reactive cells through negative selection to avoid autoimmunity.
What is the first step in pre-B cell development?
Heavy chain (H chain) genes rearrange first, producing the μ chain
What forms the pre-B cell receptor (pBCR)?
μ chain associates with Igα and Igβ and is expressed with the surrogate light chain (VpreB and λ5 genes).
What happens after pBCR formation?
Light chains rearrange and displace the surrogate light chains to form the IgM BCR.
What is the function of the pre-BCR?
Delivers a signal that the H chain is functional.
No antigen (Ag) is required for this signal.
What effects does the pre-BCR signal have?
- Turns off RAG1 and RAG2 genes.
- Initiates 5-6 rounds of cell division.
- Stops surrogate light chain expression
- Reactivates RAG1 and RAG2 for light chain rearrangement
Why are Ig gene rearrangements error-prone?
If cells fail to productively rearrange H and L chains, they die by apoptosis.
How are pre-B cells with non-productive light chain rearrangements rescued?
Up to 10 further rearrangements can occur at the κ locus before switching to the λ locus.
Why do more B cells express κ light chains than λ?
κ gene rearrangement occurs before λ gene rearrangement.
What do immature B cells express on their surface?
Membrane-bound IgM only.
What happens to immature b cells that bind multivalent self-antigens?
Undergo clonal deletion (apoptosis)
Or undergo receptor editing (light chain rearrangement for another chance)
What happens to immature B cells that bind soluble self-antigens?
They become unresponsive (anergic)
Where do T cells originate and develop?
Originate in the bone marrow stem cells.
Develop in the thymus
What processes occur during T cell development?
- Rearrange receptor genes (e.g. TCR)
- Express the pre-T receptor
- Eliminate self-reactive T cells through negative selection
What are alternative T cell lineages?
αβ TCR-expressing cells (CD4⁺ or CD8⁺).
γδ TCR-expressing cells.
What is the thymus, and what are its features?
Bi-lobed organ in the anterior mediastinum.
Contains lobules with an outer cortex and inner medulla.
Cell types: lymphoid cells, epithelial cells, macrophages, and dendritic cells
What happens during T cell maturation in the thymus?
- Pro-thymocytes enter the cortex via blood vessels.
- Rearrange TCRβ genes and express the pre-T cell receptor.
- Proliferate and rearrange TCRα genes.
- Express TCR with CD3, CD4, and CD8 markers (double-positive stage).
What is the TCR complex?
TCR requires the CD3 complex, consisting of:
δ, ε, γ chains.
ζ chain dimer (signal transduction to the nucleus).
What is positive selection in T cells?
- ensures T cells recognise self-MHC molecules with self-peptides
- occurs in the thymic cortex
- T cells that fail to recognise self-MHC die via apoptosis
What is negative selection in T cells?
Eliminates T cells that bind self-MHC + self-peptides with high affinity (to prevent autoimmunity).
Occurs in the thymic medulla.
How do positivie and negative selection create a functional T cell repertoire?
Positively selected T cells recognise self-MHC with low affinity
T cells with the highest affinity for self-MHC/self-peptide are eliminated
What is the ultimate goal of T cell selection?
Generate T cells with low affinity for self-MHC/self-peptides to avoid autoimmunity.
Retain cells likely to have high affinity for self-MHC when presenting foreign peptides.
What types of T cells exit the thymus?
CD8⁺ T cells: Recognize antigens in association with MHC class I.
CD4⁺ T cells: Recognize antigens in association with MHC class II.
How are γδ T cells different from αβ T cells?
Do not express CD4 or CD8 markers.
Less diverse TCR repertoire.
Found mostly in epithelial tissues and mucosal surfaces.
What determines lineage commitment to γδ or αβ T cells?
Successful rearrangement of either γδ or αβ TCR genes first.
