lecture 12 B cell generation

Question 1

Where does B cell development occur, what process follows immediately?

Answer 1

In the bone marrow, it is followed by negative selection (selection of non-self reactive B cells which also occurs in the bone marrow

Question 2

Describe the development process of common lymphoid progenitors

Answer 2

• FLT3 signalling required for CLP generation
• Chemokine CXCL12 acts to keep multipotent progenitor cell and CLP close to stromal cells to allow interactions
• Develops IL-7 receptor, which is a critical cytokine that provides survival signals to the developing B cells
• CAMS, VCAMS and VLA4 interactions act as anchors

Question 3

Describe the development process of early pro B-cells

Answer 3

Early pro-B cell activation due to binding of tyrosine kinase (Kit) to stem cell factor (SCF) inducing Kit kinase activity (phosphorylation)

Question 4

How does a late pro-b cell become an immature B cell

Answer 4

LPBC binds Il-7, becomes pre-B cell
pre-B expresses H chain as part of the pre-B cell receptor and ceases to express Kit
Becomes immature B cell which now expresses H and L chain to make IgM

Question 5

What are the 2 stages of pre-b cells? What does the receptor do?

Answer 5

Large pre-B and small pre-B
Large 1st - where pre B cell receptor expression occurs, where it contains heavy IgM chain expression and surrogate light chain, no a fully mature antibody bc only surrogate
Signals to cell to stop HCG rearrangement and start making light chain gene rearrangement to allow development of the small pre-B cell

Question 6

What is the surrogate light chain

Answer 6

Makes something that looks like a light chain, composed of 2 different genes that make proteins that stick together to make it (VpreB, variable like, and lamda-5, constant like)
Helps stabilize heavy chain on surface of pre-B cell

Question 7

What is the significance of the Ig-alpha-Ig-beta heterodimer in the context of B cell generation

Answer 7

Expressed from pro B cell to mature B cell stage
In pre B cells it provides signal to stop H chain rearrangeemnt and start L chain
In mature its required for signalling when antigen binds antibody

Question 8

What is the major difference between an immature and mature B cell

Answer 8

Immature
Rearranged, mu heavy chain is produced in membrane form amd kappa or lamda expression to form IgM expression
No longer expressing surrogate light chains
Mature
IgD expression in secondary lymph organs when released from the bone marrow
Alternative splicing yields mu and delta mRNA

Question 9

What is B cell development dependent on and how does that relate to allelic exclusion?

Answer 9

Depends on the sequential productive rearrangement of H chain and L chain genes
Allelic exclusion is the process by which only one allele of a gene is expressed while the other allele is silenced, producing single antigenic specificity

Question 10

describe allelic exclusion

Question 11

What is the difference between clonal deletion and receptor editing, how do they contribute to B cell development

Answer 11

Both occur in the marrow at the immature B cell stage
Clonal deletion is the removal of self reactive B cells, resulting in apoptosis
Receptor editing is further gene rearrangements (V to J) via active RAG enzymes and available L chain alleles resulting in the replacement of existing light chain and altered specificity so its no longer auto reactive