B cell Development

Question 1

Where do B cells develop?

Answer 1

Hematopoietic stem cells in the bone marrow, which express the PAX5 transcription factor

Question 2

How many B cells are produced daily?

Answer 2

~3 × 10¹⁰ B cells per day.

Question 3

What processes are involved in B cell development?

Answer 3

• 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.

Question 4

What is the first step in pre-B cell development?

Answer 4

Heavy chain (H chain) genes rearrange first, producing the μ chain

Question 5

What forms the pre-B cell receptor (pBCR)?

Answer 5

μ chain associates with Igα and Igβ and is expressed with the surrogate light chain (VpreB and λ5 genes).

Question 6

What happens after pBCR formation?

Answer 6

Light chains rearrange and displace the surrogate light chains to form the IgM BCR.

Question 7

What is the function of the pre-BCR?

Answer 7

Delivers a signal that the H chain is functional.
No antigen (Ag) is required for this signal.

Question 8

What effects does the pre-BCR signal have?

Answer 8

1. Turns off RAG1 and RAG2 genes.
2. Initiates 5-6 rounds of cell division.
3. Stops surrogate light chain expression
4. Reactivates RAG1 and RAG2 for light chain rearrangement

Question 9

Why are Ig gene rearrangements error-prone?

Answer 9

If cells fail to productively rearrange H and L chains, they die by apoptosis.

Question 10

How are pre-B cells with non-productive light chain rearrangements rescued?

Answer 10

Up to 10 further rearrangements can occur at the κ locus before switching to the λ locus.

Question 11

Why do more B cells express κ light chains than λ?

Answer 11

κ gene rearrangement occurs before λ gene rearrangement.

Question 12

What do immature B cells express on their surface?

Answer 12

Membrane-bound IgM only.

Question 13

What happens to immature b cells that bind multivalent self-antigens?

Answer 13

Undergo clonal deletion (apoptosis)
Or undergo receptor editing (light chain rearrangement for another chance)

Question 14

What happens to immature B cells that bind soluble self-antigens?

Answer 14

They become unresponsive (anergic)

Question 15

Where do T cells originate and develop?

Answer 15

Originate in the bone marrow stem cells.
Develop in the thymus

Question 16

What processes occur during T cell development?

Answer 16

1. Rearrange receptor genes (e.g. TCR)
2. Express the pre-T receptor
3. Eliminate self-reactive T cells through negative selection

Question 17

What are alternative T cell lineages?

Answer 17

αβ TCR-expressing cells (CD4⁺ or CD8⁺).
γδ TCR-expressing cells.

Question 18

What is the thymus, and what are its features?

Answer 18

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

Question 19

What happens during T cell maturation in the thymus?

Answer 19

1. Pro-thymocytes enter the cortex via blood vessels.
2. Rearrange TCRβ genes and express the pre-T cell receptor.
3. Proliferate and rearrange TCRα genes.
4. Express TCR with CD3, CD4, and CD8 markers (double-positive stage).

Question 20

What is the TCR complex?

Answer 20

TCR requires the CD3 complex, consisting of:
δ, ε, γ chains.
ζ chain dimer (signal transduction to the nucleus).

Question 21

What is positive selection in T cells?

Answer 21

• 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

Question 22

What is negative selection in T cells?

Answer 22

Eliminates T cells that bind self-MHC + self-peptides with high affinity (to prevent autoimmunity).

Occurs in the thymic medulla.

Question 23

How do positivie and negative selection create a functional T cell repertoire?

Answer 23

Positively selected T cells recognise self-MHC with low affinity
T cells with the highest affinity for self-MHC/self-peptide are eliminated

Question 24

What is the ultimate goal of T cell selection?

Answer 24

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.

Question 25

What types of T cells exit the thymus?

Answer 25

CD8⁺ T cells: Recognize antigens in association with MHC class I.
CD4⁺ T cells: Recognize antigens in association with MHC class II.

Question 26

How are γδ T cells different from αβ T cells?

Answer 26

Do not express CD4 or CD8 markers.
Less diverse TCR repertoire.
Found mostly in epithelial tissues and mucosal surfaces.

Question 27

What determines lineage commitment to γδ or αβ T cells?

Answer 27

Successful rearrangement of either γδ or αβ TCR genes first.