Activated B cells and how they change it up

Question 1

what is Bruton’s tyrosine kinase deficiency?

Answer 1

Brutons disease or X-linked agammaglobulinemia
- low or completely absent Igs in blood
- Btk gene is on the X-chromosome

Question 2

what are the effects of Bruton’s tyrosine kinase deficiency?

Answer 2

-Btk phosphorylates and activates PLCg2

Absence causes
- No proliferation of B cells
- No activation of B cells
- No mature B cells

Question 3

what are the symptoms of Bruton’s tyrosine kinase deficiency?

Answer 3

Frequent infections, delayed growth

Question 4

what is the treatment for burton’s tyrosine kinase deficiency?

Answer 4

regular intravenous gamma globulin, prompt treatment of any cuts/infections

Question 5

what is Igalpha deficiency?

Answer 5

agammaglobulinaemia
- this is not X-linked

Question 6

what are the symptoms of Igalpha deficiency?

Answer 6

frequent infections, delayed growth

Question 7

what is the treatment for Igalpha deficiency?

Answer 7

regular intravenous gamma globulin, prompt treatment of any cuts/infections

Question 8

what are the four phases of B cell development?

Answer 8

1. B cell precursors rearrange Ig genes
2. Immature B cell bound to self Ag is removed
3. Mature B cells bound to foreign antigen is activated
4. activated B cells give rise to plasma and memory cells

Question 9

where do BCR form?

Answer 9

In the bone marrow

Question 10

where does B cell negative selection occur?

Answer 10

In the bone marrow

Question 11

where do B cells go once they are activated?

Answer 11

mature B cells migrate to the periphery

Question 12

where does antibody secretion and memory cells go?

Answer 12

in the bone marrow and lymphoid tissue

Question 13

what B cell types can develop independent of antigen?

Answer 13

Stem cell
Pro B cell
pre B cells

Question 14

what B cell types need antigen to develop?

Answer 14

immature B cell
mature B cell
germinal centre B cell
memory B cell
plasma cell

Question 15

what is the germinal centre made up from?

Answer 15

mostly composed of proliferating B cells and ~10% antigen specfic T cells

Question 16

how does the germinal centre change during infection?

Answer 16

It is dynamic
- grows as the immune response increases, shrinks and disappears when infection is cleared

Question 17

what are the structure of a transverse section of white pulp?

Answer 17

-Germinal centre
- B-cell carcinoma
- Marginal zone
- Perifollicular zone
Central arteriole
periarteriolar lymphoid sheath
-red pulp

Question 18

why does IgM form a pentameric structure?

Answer 18

More binding sites for antigen meaning antigen is more likely to bind and the signal to be sufficient to start an immune response as IgM is the initiat antibody produced

Question 19

what is antibody class switching?

Answer 19

Cytokines can induce RNA transcript production in “switch regions” near the heavy chain segment they preferentially induce

Question 20

when does a B cell start secreting IgM?

Answer 20

once it interacts with antigen

Question 21

what is the function of the switch region of B cells that regulates antibody class?

Answer 21

Special switch region sequences cause formation of secondary DNA structures that promote pausing of RNA polymerase II and binding of activation induced cytidine deaminae (AID)

Question 22

what is AID?

Answer 22

only produced on activated B cells
- can induce class switching of antibody
(AID can only bind ssDNA)

Question 23

what does AID drive?

Answer 23

somatic hypermutation and class switch recombination

Question 24

what are the regions of antibody?

Answer 24

• Antigen binding site
• Variable region
• Constant region

Question 25

when does somatic hypermutation occur?

Answer 25

Occurs after antigen-driven B cell activation as part of the germinal centre response

Question 26

what is somatic hypermutation?

Answer 26

Introduction of point mutations - A 50% chance at each division that a B cell will acquire a mutation in antibody it encodes

Question 27

what is the function of somatic hypermutation?

Answer 27

- Allows more diversity in the antibody region - Some increase antigen binding strength - Some decrease antigen binding strength The higher binding antibody outcompetes the others

Question 28

what is AID?

Answer 28

Activation induced cytidine deaminase (AID)

Question 29

what is the role of AID in somatic hypermutation?

Answer 29

Deaminates DNA - leads to base pair mismatches - lesion repair induces mutations - Doesn't have the same sequences that stall RNA polymerase II as switch regions do - Mechanism for RNA pol II stalling is unknown

Question 30

where does somatic hypermutation occur?

Answer 30

Point mutations are induced into rearranged variable regions at a high rate - occurs at "hotspots" in the genes

Question 31

what is the role of 3' enhancers in somatic hypermutation?

Answer 31

Enable chromosomal looping - this forms transcriptional domains that control transcriptional levels enabling AID to bind - Without the 3' enhancers there is no somatic hypermutation, no class switch recombination

Question 32

what are the important things that help somatic hypermutation?

Answer 32

RNA polymerase II pausing is necessary to allow AID to bind and introduce a lesion, and the 3' enhances are critical to drive the high levels of transcription that start the process