B-cell development

Question 1

B cells are generated in the ?

Answer 1

Bone marrow

Question 2

B cell development begins in the ———- and is completed in the ——-

Answer 2

B cell development begins in the Bone Marrow and is completed in the periphery (Spleen)

Question 3

Chracterstics of Early pro-B cells and Late pro-B cells

Answer 3

Early pro-B:
* H-chain genes–> D-J rearranging
* Surface IgG–> Absent

Late pro-B:
* H-chain genes –> V-DJ rearranging
* Surface IgG –> Absent

Question 4

features of Large pre-B cells and Small Pre-B cells

Answer 4

Large/small pre-B-cells:
* H-chain genes –> VDJ rearranged
* Surface IgG –> intracelluar μ-chain

Question 5

Characteristics of Immature B-cells

Answer 5

IgM expressed on cell surface
H-chain genes –> VDJ rearranged

Question 6

Charactersitics of Mature B cells

Answer 6

IgM and IgD expressed on cell surface
H-chain genes –> VDJ rearranged

Question 7

Steps of B cell development in the bone marrow

Answer 7

1) Pro-B cells
* D-JH recombination
* Promotes VH to DJH recombination initiation
* Expressionof CD19,CD20,CD21and Igα and Igβ begins

2) Pre-B cells
* Heavy chain rearrangement is finalized
* Ig heavy chain complexed with a surrogate light chain which results in pre-BCR expression
* Late pre-B stage marked by initiation of light chain gene rearrangement

3) Immature B cells
* Completion of light chain rearrangement
* IgM receptor is expressed on the cell surface first

4) Mature B cells:
* Expression of IgM and IgD on the cell surface

Question 8

B cell maturation depends on rearrangement of the ——-

Answer 8

Ig DNA

Question 9

Explain how Pro-B cells become Pre-B cells

Answer 9

1) pro-B cell is a D-J rearrangement of the heavy chain followed by V-DJ (V-DJ rearranging)
2) Upon completion of heavy chain rearrangementthe cell is classified as a pre-B (VDJ rearranged)
3) Continued development requires productive rearrangement of a light chain

Question 10

how are Pre-BCR formed

Answer 10

1) Heavy chains are recombined and expressed first (Expression of a functional heavy chain shuts down recombination machinery temporarily)
2) The heavy μ chain is paired with a Surrogate light chain (a V-like sequence called Vpre-B and a C-like sequence called λ5)
3) This molecule appears on the cell surface together with the Igα/Igβ heterodimer to form the pre-B-cell receptor

    * the Pre-BCR gives important signalling which regulates allelic exclusion

Question 11

What is allelic exclusion

Answer 11

Pre-BCR provide signaling which ensures that each B cell synthesise only one heavy and one light chain

Question 12

Fxn of Pre-BCR is B cell development

Answer 12

1) Allelic exclusion
2) Induces the recombination of the Light-chain
3) Induce survival and proliferation

Question 13

Immature B cells bearing autoreactive BCR that react strongly with self-antigen are ———– through Apoptosis (————–)

Answer 13

Immature B cells bearing autoreactive BCR that react strongly with self-antigen are clonally deleted through Apoptosis (Central tolerance)

Question 14

How are escaping Autoreactive B-cells (from the BM) inactivated by the immune system?

Answer 14

Autoreactive B cells that escape negative selection in the bone marrow are inactivated in the periphery (anergy) and become anergic which means non-functional

• This is known as Peripheral Tolerance

Question 15

Anergic B cells express high levels of —- which renders them inactive

Answer 15

IgD

Question 16

Immature B cells express ?

Answer 16

mIgM

Question 17

Fully mature B cells express?

Answer 17

mIgM and mIgD

Question 18

How are B cells activated

Answer 18

they require T cells to become activated–> once activated they express high levels of IgM/IgD