Genetics Of Bcr/antibodies Flashcards
What is another word for antibody specification
Antibody repertoire
Does each lymphocyte have a specific bcr
Yes
Which regions on a bcr/antibody are encoded by several gene segments which recombine
Variable regions vh and vl
What is dna recombination of gene segments in the variable region called
Somatic dna recombination
How are there more bcr than genes
Because of many gene segments and their recombination for variable region
Are variable and constant regions encoded by diff gene segments in both tcr and bcr
Yes
Which 3 gene segments which has many copies encode for Vh chain on bcr and the Va chain on tcr
V d and j
Which gene segments encode for Vl on bcr and vb on tcr
V and j
When does gene segment recombination occur in B cells
B cell development in bone marrow
What type of recombination is somatic dna recombination
NHEJ
Non homologous end joining recombination
Explain briefly how the vl region comes about via v and j gene segments
Dna breaks in nhej recombiantion bring v and j segments close together to form Vl
This then joins the cL gene
In vh recombiantion, which gene segments must recombine first
D and J
Then they bind with V gene segment
Does light chain rearrangement need to wait till after heavy chain rearrangement NHEJ recombiantion
Yes
Which light chain gene is rearranged first via v and j
Kappa
When does lamda light chain get rearranged
If rearrangement of kappa doesn’t work
Why do heavy chains have larger variability
More gene segments vdj
Is there only 1 type of v d and j or many different genes which causes variability
Many different types. The recombination is random between them
Kappa and lamda light chain are at diff loci. What Chromosome is each on
Kappa - 2
Lamda - 22
How is lamda locus on chr 22 arranged for somatic dna recombination
Has the different v segments
Followed by different j segments , each having 1 constant lamda segment
How is kappa locus on chr 2 arranged
Has the different v gene segments
Followed by j segments
Then a constant kappa gene
Which chromosome is heavy ig chain on and how is it arranged
Chr 14
Different v gene segments
Then d segments
Then J segments
Followed by constant mu,delta,gamma etc for isotope determination
What type of sequence on vdj genes determines recombination (not random)
Recombination signal sequences RSS
Which genes encode for a protein complex which is important in NHEJ recombination at RSSs
Rag 1 and rag 2
Which important enzyme does rag 1 and rag 2 encode for in the protein complex and what does it do
Recombinase
Allows dna cutting at recognition signal sequences
What does rag stand for
Recombination activating genes
Cleavage at RSS leaves hairpins of dna after V and D. What happens next
They are cleaved
What happens once dna at ends of v and d are cleaved
TdT is recruited which adds nucleotides and then ligase in the rag complex joins v and d
Terminal deoxynucleotidyl transferase
What is diversity of gene segments/V regions through random joining via terminal transferase tdt called
Junctional diversity
Why and how does rearrangements via NHEJ recombiantion only occur on 1 chromosome (allele exclusion)
Rearrangement stops after it occurs in both heavy and light variable regions
Ensures B cells to have 1 specific bcr
What is combinatorial diversity
Rearrangements of diff v d and j segments randomly
What is mutation in vdj after antigen recognition called
Somatic hypermutation
What enzyme is involved in somatic hypermutation of vdj after antigen recognition
AID
Activation induced deaminase
What does activation induced deaminase aid do to cause somatic hypermutation
Deaminates cytosine into uracil which is recognised by error prone repair systems causing mutation
Where does somatic hypermutation allow for increased variability of bcr
In germinal centres
Is vdj altered between bcr and antibody release
No
What encodes different constant regions on isotypes of antibodies
C region gene segment
Eg cmu c delta c gamma c alpha
There are 4 igG subclasses so how many c region segments are there
4 c gamma segments
Why is constant region mu for igm first expressed
Because closest to vdj on chr 14
Which antibody c region segment is closest to vdj after igm
Igd
Why are igm and igd often coexpressed
Differential rna processing
What are the regions called which allow class switching recombination
Switch regions
Which enzyme allows class switching recombination at switch regions
AID
Activation induced deaminase
In presence of what does activation induced deaminase cause class switching
Cytokines
Explain briefly how class switching at switch regions occurs Eg for igd expression
Loop dna with c mu and then cleave it bringing igd close to vdj
Igm can never be expressed again in that cell
What is expressed after delta c
C gamma then c alpha
