Lecture 17 - Lymphocyte Development - B Cells

Question 1

Where do B cells mature in birds?

Answer 1

Bursa of fabricus

Question 2

Where do B cells mature in humans?

Answer 2

Bone marrow

Question 3

State of BCR in an immature B cell

Answer 3

Fully mature BCR

Question 4

Why are there fewer BCR expressed than possible gene rearrangements?

Answer 4

V(D)J recombination is not completely random, hence why there are ~10^6 expressed BCR, and 10^11 theoretical combinations of V(D)J genes

Question 5

From what do all lymphocytes arise?

Answer 5

Uncommitted progenitors

Question 6

Granulocytes arising from granulocyte myeloid progenitor
1)
2)
3)
4)
5)

Answer 6

1) Neutrophil
2) Eosinophil
3) Basophil
4) Monocyte
5) Unknown mast cell precursor

Question 7

Is the multipotent progenitor self-renewing?

Answer 7

No

Question 8

Function of stromal cells

Answer 8

Secretes factor essential for B cell maturation

Question 9

Stromal cell location

Answer 9

Bone marrow

Question 10

Where in the bone marrow is the multipotent progenitor?

Answer 10

Endosteum

Question 11

How is B cell development location-dependent?

Answer 11

Stromal cells secrete different factors required for B cell development in different places in the bone marrow.

B cells become more mature as they move from the endosteum into the central sinus

Question 12

When is the heavy mu chain produced?

Answer 12

Recombined in pre-pro and pro B cells
Expressed on pre-B cells
Pre-B cells that don’t produce mu chains die

Question 13

What induces surrogate light chain assembly?

Answer 13

E2A-induced lambda 5

Question 14

Components of the surrogate light chain

Answer 14

VpraB, Igalpha, Igbeta, SLC

Question 15

How does signalling through the pre-BCR occur?

Answer 15

Pre-BCR dimerisation/oligomerisation

Question 16

Important enzyme in pre-BCR signalling

Answer 16

Bruton’s tyrosine kinase

Question 17

Interleukin that is essential for B cell development

Answer 17

IL-7

Question 18

What happens at the conclusion of heavy-chain rearrangement?

Answer 18

Pre-b cell large expands 30-60-fold before transitioning to resting pre-B cell small

Question 19

Consequence of expansion of pre-B cell large before transitioning to small

Answer 19

Large number of pre-B cell small with identical heavy chains

Question 20

What is a B cell only being able to express kappa or lamba light chain called?

Answer 20

Isotypic exclusion

Question 21

What happens in the transition between pre-B cell small and immature B cell?

Answer 21

IgM is expressed

Question 22

Is antigen needed for pre-BCR to be engaged?

Answer 22

No

Question 23

Number of attempts at heavy chain recombination

Answer 23

Two

Because of allelic exclusion

Question 24

Number of attempts at light chain recombination

Answer 24

Four

Because of allelic exclusion and kappa and lambda loci

Question 25

When does Bruton’s X-linked agammaglobulinaemia present?

Answer 25

~3 months after birth

Question 26

RAG expression during B cell development

Answer 26

Two peaks

1) Early pro-B cell
2) Pre-B cell

Question 27

What ensures that a B cell can only make one type of antibody?

Answer 27

Allelic exclusion

Question 28

Negative selection/Clonal deletion

Answer 28

If an immature B cell encounters a strongly-cross-linking antigen in the bone marrow

Only self antigens should be in the bone marrow

Question 29

What can save an immature B cell from clonal deletion?

Answer 29

RAG is still active at the stage of immature B cell, and can initiate receptor editing

Question 30

Stages of B cell development where heavy chain locus is rearranged

Answer 30

Early, late pro-B

Question 31

Stage of Bc ell development where light chain locus is rearranged

Answer 31

Pre-B

Question 32

Signals without which immature B cells will die

Answer 32

Positive signals