L12 - Molecular and Cellular Aspects of Early Lymphocyte Activation - B Cells

Question 1

What is allelic exclusion?

Answer 1

The process by which one gene is expressed while the other one is silent. Applies to B-cells

Question 2

Where do B-cells develop?

Answer 2

Bone marrow, but can also develop in neonatal spleen and liver

Question 3

How does the generation of B-cells throughout life differ from T-cells?

Answer 3

B cells develop continuous throughout life unlike T cells

Question 4

What cells eventually give rise to the cells that develop into pre B-cells and what cells are these?

Answer 4

Hematopoietic stem cells -> Multipotent progenitors -> Common lymphocyte progenitor

Question 5

What are positive signals in reference to lymphocyte development?

Answer 5

Cells that do not receive signals will die. Helps keep immune system in check

Question 6

What goes before: pre or pro?

Answer 6

Pro

Question 7

How do Pro-B cells determine if the new μ-chain (heavy chain) is viable?

Answer 7

Forms a pre-BCR by pairing with surrogate chains, E2A induced λ5, Vpreβ; Igα, Igβ. These form pre-BCR

Question 8

What happens if pre-BCR is successful?

Answer 8

The cell is now considered pre-B cells. This is an important checkpoint that mediates transition from pro B cells to pre B cells

Question 9

What is CD25 and what is its significance?

Answer 9

The IL2-α chain. Pre-BCRs induce expression of CD25
- IL2 receptor is much better at signalling when integrated with α chain > higher affinity, responsible for B-cell proliferation

Question 10

What is the signifiance of B-cell proliferation following CD25?

Answer 10

Good heavy chains don’t go to ‘waste’. Is the reason why heavy chains aren’t as diverse
- Large pre-B cells expand 30-60 fold before transitioning into smaller resting pre-B cells leading to many with identical heavy chains

Question 11

How many ‘chances’ does the pre-B-cell have to rearrange the light chain?

Answer 11

4. 2 alleles (κ and λ) and 2 loci

Question 12

How does negative selection of B-cells occur?

Answer 12

If an immature B-cell encounters a strongly cross-linking antigen in bone marrow, cell dies. RAG can rescue via continuous light chain rearrangements however

Question 13

Why is it important for some immature B-cells to become anergic to self rather than deletion?

Answer 13

Some pathogens have evolved to express surface proteins very similar to self, a lot of overlap

Question 14

What light chain is rearranged first?

Answer 14

κ gene