Genetics Of Bcr/antibodies

Question 1

What is another word for antibody specification

Answer 1

Antibody repertoire

Question 2

Does each lymphocyte have a specific bcr

Answer 2

Yes

Question 3

Which regions on a bcr/antibody are encoded by several gene segments which recombine

Answer 3

Variable regions vh and vl

Question 4

What is dna recombination of gene segments in the variable region called

Answer 4

Somatic dna recombination

Question 5

How are there more bcr than genes

Answer 5

Because of many gene segments and their recombination for variable region

Question 6

Are variable and constant regions encoded by diff gene segments in both tcr and bcr

Answer 6

Yes

Question 7

Which 3 gene segments which has many copies encode for Vh chain on bcr and the Va chain on tcr

Answer 7

V d and j

Question 8

Which gene segments encode for Vl on bcr and vb on tcr

Answer 8

V and j

Question 9

When does gene segment recombination occur in B cells

Answer 9

B cell development in bone marrow

Question 10

What type of recombination is somatic dna recombination

Answer 10

NHEJ

Non homologous end joining recombination

Question 11

Explain briefly how the vl region comes about via v and j gene segments

Answer 11

Dna breaks in nhej recombiantion bring v and j segments close together to form Vl

This then joins the cL gene

Question 12

In vh recombiantion, which gene segments must recombine first

Answer 12

D and J

Then they bind with V gene segment

Question 13

Does light chain rearrangement need to wait till after heavy chain rearrangement NHEJ recombiantion

Answer 13

Yes

Question 14

Which light chain gene is rearranged first via v and j

Answer 14

Kappa

Question 15

When does lamda light chain get rearranged

Answer 15

If rearrangement of kappa doesn’t work

Question 16

Why do heavy chains have larger variability

Answer 16

More gene segments vdj

Question 17

Is there only 1 type of v d and j or many different genes which causes variability

Answer 17

Many different types. The recombination is random between them

Question 18

Kappa and lamda light chain are at diff loci. What Chromosome is each on

Answer 18

Kappa - 2

Lamda - 22

Question 19

How is lamda locus on chr 22 arranged for somatic dna recombination

Answer 19

Has the different v segments

Followed by different j segments , each having 1 constant lamda segment

Question 20

How is kappa locus on chr 2 arranged

Answer 20

Has the different v gene segments

Followed by j segments

Then a constant kappa gene

Question 21

Which chromosome is heavy ig chain on and how is it arranged

Answer 21

Chr 14

Different v gene segments

Then d segments

Then J segments

Followed by constant mu,delta,gamma etc for isotope determination

Question 22

What type of sequence on vdj genes determines recombination (not random)

Answer 22

Recombination signal sequences RSS

Question 23

Which genes encode for a protein complex which is important in NHEJ recombination at RSSs

Answer 23

Rag 1 and rag 2

Question 24

Which important enzyme does rag 1 and rag 2 encode for in the protein complex and what does it do

Answer 24

Recombinase

Allows dna cutting at recognition signal sequences

Question 25

What does rag stand for

Answer 25

Recombination activating genes

Question 26

Cleavage at RSS leaves hairpins of dna after V and D. What happens next

Answer 26

They are cleaved

Question 27

What happens once dna at ends of v and d are cleaved

Answer 27

TdT is recruited which adds nucleotides and then ligase in the rag complex joins v and d

Terminal deoxynucleotidyl transferase

Question 28

What is diversity of gene segments/V regions through random joining via terminal transferase tdt called

Answer 28

Junctional diversity

Question 29

Why and how does rearrangements via NHEJ recombiantion only occur on 1 chromosome (allele exclusion)

Answer 29

Rearrangement stops after it occurs in both heavy and light variable regions

Ensures B cells to have 1 specific bcr

Question 30

What is combinatorial diversity

Answer 30

Rearrangements of diff v d and j segments randomly

Question 31

What is mutation in vdj after antigen recognition called

Answer 31

Somatic hypermutation

Question 32

What enzyme is involved in somatic hypermutation of vdj after antigen recognition

Answer 32

AID

Activation induced deaminase

Question 33

What does activation induced deaminase aid do to cause somatic hypermutation

Answer 33

Deaminates cytosine into uracil which is recognised by error prone repair systems causing mutation

Question 34

Where does somatic hypermutation allow for increased variability of bcr

Answer 34

In germinal centres

Question 35

Is vdj altered between bcr and antibody release

Answer 35

No

Question 36

What encodes different constant regions on isotypes of antibodies

Answer 36

C region gene segment

Eg cmu c delta c gamma c alpha

Question 37

There are 4 igG subclasses so how many c region segments are there

Answer 37

4 c gamma segments

Question 38

Why is constant region mu for igm first expressed

Answer 38

Because closest to vdj on chr 14

Question 39

Which antibody c region segment is closest to vdj after igm

Answer 39

Igd

Question 40

Why are igm and igd often coexpressed

Answer 40

Differential rna processing

Question 41

What are the regions called which allow class switching recombination

Answer 41

Switch regions

Question 42

Which enzyme allows class switching recombination at switch regions

Answer 42

AID

Activation induced deaminase

Question 43

In presence of what does activation induced deaminase cause class switching

Answer 43

Cytokines

Question 44

Explain briefly how class switching at switch regions occurs Eg for igd expression

Answer 44

Loop dna with c mu and then cleave it bringing igd close to vdj

Igm can never be expressed again in that cell

Question 45

What is expressed after delta c

Answer 45

C gamma then c alpha