B cells: germinal centre

Question 1

Recap - diversity in Hla molecules

Answer 1

Polymorphism
Polygeny

Question 2

Recap - diversity in tcrs

Answer 2

Combinatorial diversity
Junctional diversity
Pairing - alpha beta

Question 3

Recap - diversity in bcrs/igs

Answer 3

Primary diversification = combinatorial diversity, junctional diversity, combo of h and l chains
Secondary diversification = somatic hypermutation, class switching

Question 4

Name zones of germinal centre

Answer 4

Dark zone
Light zone

Question 5

Describe light zone germinal centre

Answer 5

Tfh found here
Follicular dcs retain ag in light zone (to give signal 1 and 2 again)

Question 6

What happens in germinal centre - gen

Answer 6

Dynamic and complex

Question 7

What happens in germinal centre = B cells that enter germinal centre

Answer 7

Have already encountered ag - signal 1 and have been activated by a T cell at t-b border and proliferated = goes to germinal center
Have ability to produce igm/igd of a baseline affinity - transmembrane

Question 8

What are the 2 things that happen in germinal centre

Answer 8

Somatic hypermutation
Clsss switching

Question 9

Describe somatic hypermutation in germinal centre

Answer 9

Affinity for ag improved

Question 10

Describe class switching in germinal centre

Answer 10

Form igd/m to igg iga ige
Ag specificity the same

Question 11

What happens primarily in light zone

Answer 11

Primary site of plasma and memory cell differentiation = become either one

Question 12

Dark zone is the site of

Answer 12

Somatic hypermutation

Question 13

Describe follicular dendritic cells role

Answer 13

Ag concentration sites for future selection and differentiation - bc retained ag

Question 14

Describe B cells interacting with tfh = in germinal center

Answer 14

= provides conditions for differentiation (signal 1 and 2 again), memory cell production and class switching

Question 15

What happens to B cells in dark zone

Answer 15

Undergo somatic hypermutation —> cells with same specificity but diff affinity

Question 16

What happens after B cells somatic hypermutation in dark zone

Answer 16

Resulting B cells migrate to light zone where they compete to bind ag trapped on follicular dc

Question 17

Describe what types of B cells will bind/not bind ag

Answer 17

Higher affinity B cell = binds ag —> signal 1, internalizes ag:bcr and processes it to present on mhc2 (affinity maturation)
Lower affinity B cells fail to bind ag —> do not receive signal 1 and die by apoptosis

Question 18

What happens after B cell binds ag

Answer 18

B cells that process ag and present it on mhc2 can interact with tfh *linked recognition
Signal received via cd40 - signal2

Question 19

What produces class switching

Answer 19

B cells receive cytokines from tfh —> class switching
= informs the type of ab B cell is going to produce

Question 20

What can happen after class switching

Answer 20

B cells can then re enter dark zone and undergo more somatic hypermutation

Question 21

What are the 2 outcomes of germinal centre

Answer 21

Plasma cells or memory B cells

Question 22

Describe plasma cells

Answer 22

Stop expresssing high levels bcr
Secrete ig of same specificity as bcr of their progenitor B cell
Should bind ag with higher affinity
Secreted ig can be iga,ige, igg

Question 23

Describe memory B cells

Answer 23

Express high levels bcr
Bcr has same specificity as progenitor B cell
Bcr should have higher affinity for ag

Question 24

What is aid - somatic hypermutation

Answer 24

Activation induced cytokine deaminase = protein responsible for somatic mutations —> deaminates cytidine residues in ssdna

Question 25

What does aid do

Answer 25

Cytidine to uridine which is then removed Mismatch repair pathway + error prone polymerase activity —> incorporate any nt into nick (does not have to match - stick any nt) Produces individual point mutation in ig heavy and light chain variable regions

Question 26

Is aid always helpful

Answer 26

Nooo Some of these changes not productive = so makes affinity better or worse

Question 27

Where does somatic hypermutation happen

Answer 27

Mainly occurs in cdr loops of v regions = most variable

Question 28

Describe what somatic hypermutation leads to

Answer 28

B cells that can bind, process and present more ag to t cels for cytokine assistance survival = affinity maturation Product = increased ab affinity with increased exposure

Question 29

Where does class switching recombination happen

Answer 29

Occurs within germinal centre after ag contact - signal 2 a Second time

Question 30

Signals for class switching

Answer 30

B cells must receive costimulatory signals from cd40 to engage in classs switching recombination Which cytokine signal received determines which isotype produced

Question 31

What does class switching lead to

Answer 31

Class switching —> which heavy chain constant region is going to be selected

Question 32

Describe process of class switching

Answer 32

Recombination occurs between switch regions = one after vdj region and one upstream of constant region to be recombined Aid = nicks after vdj region and then other nick = upstream constant region we want to be recombined = everything in middle excised

Question 33

What happens when B cell received cytokine signal

Answer 33

Transcription activated upstream of constant region Opening of dsdna —> 2 ssdnas =Dna now accessible to aid = activation induced cytidine deaminase on ssdna= makes it u Nicks made on both strands on dna in switch region

Question 34

Is class switching reversible

Answer 34

No Irreversible

Question 35

Describe specifically the recombination during class switching

Answer 35

Double stranded breaks in dna upstream of constant region will be recombined Ds break repair machinery repairs break by cutting out intervening dna Selected region now adjacent to vdj region = leads to transcription, splicing, mods = get ab

Question 36

Describe memory = early re infection

Answer 36

Like less than month after primary = handled by pre formed abs/effector T cells from primary the previous response = not just using memory

Question 37

Describe memory = late reinfection

Answer 37

If years later = handled by immune memory b and T cells Fast and very effective

Question 38

What is immunological memory

Answer 38

Ability of immune system to respond more rapidly and more effectively on a second encounter with ag

Question 39

What immunological memory dependent on

Answer 39

Adaptive immune mechanisms = ag specific , memory responses occur after primary response by lymphocytes initially generated late in primary response, long lived

Question 40

What does memory lead to

Answer 40

Resistant to a particular infectious disease upon re exposure only after having had that disease one before - or after being vaccinated

Question 41

What are the differences between primary and memory responses

Answer 41

More abs, more cells Diff abs - higher affinity, diff lymphocyte features

Question 42

Describe features of immunological memory

Answer 42

Easier to detect/monitor B cells than T cells = abs can be measured in serum, memory T cells reside in tissue - do not know which tissues Mediated by a small and steady number of memory cells = some of them proliferating at a given time