Chapter 6/7: Immunoglobulin Variability

Question 1

Isotope

Answer 1

Class or subclass of Ig

Question 2

Allotype

Answer 2

Existence of alleles in Ig loci

Question 3

Framework region

Answer 3

Acts as the scaffolding for the CDR

Less variability to increase stability

Question 4

Somatic Diversification

Answer 4

Generates Ab diversity
Rearrange during B cell development from immature pre-B to mature B cell
Generates unique specificity for each cell
Leads to better affinity of B cell over time
Both heavy and light chain undergo rearrangement

Question 5

Light chain

Answer 5

Consists of V, J and C
No D region
Kappa or lamba chain

Question 6

Heavy chain

Answer 6

Consists of V, D, J and C

Question 7

RSS

Answer 7

Recombination signal sequences
Contained in DNA flanking the germline V, D, J segments
Form loops which are removed by V(D)J recombinase enzyme complex

Question 8

12/23 rule

Answer 8

Stops V to J rearrangement in the heavy chain

V to D is 23/12 whereas V to J would be 23/23

Question 9

RAG

Answer 9

Recombination activating genes
Breaking and joining of DNA
Required for rearrangement of chains

Question 10

Exonucleases

Answer 10

Involved in removal of nucleotides and ends generated by RAG’s

Question 11

TdT

Answer 11

Terminal deoxynucleotide transferases
Insertion of random non template encoded nucleotides
Creates N regions

Question 12

N regions

Answer 12

Imprecise joining of the V-D, D-J gene segments because of deletion and insertion
Contribute to diversity
Failure of rearrangement (but diversity is more important so some failure can happen)

Question 13

Combinatorial Joining

Answer 13

Source of diversity

Different combinations of V, D, J for a particular chain

Question 14

Combinatorial association

Answer 14

Different combinations of heavy and light chains

Question 15

Junctional diversity

Answer 15

Contributes to diversity

Contributes to random N region sequences

Question 16

Somatic mutation

Answer 16

Creates diversity as immune response progresses or matures
E.g. affinity
Mostly found in the secondary response

Question 17

Antibody maturation sources

Answer 17

Isotope switching
Affinity maturation (involves somatic mutations)
Both use AID not RAG

Question 18

Isotope switching mechanism

Answer 18

Regulated by switch regions
Forms loops, regions in loops excised, following region (e.g. gamma) is the isotope it will switch to
Switching is permanent

Question 19

IgM/IgD Selection

Answer 19

Regulated by RN splicing

Can splice to mu or delta

Question 20

Transmembrane/secreted Ig mechanism

Answer 20

Involves alternate splicing
Membrane anchor encodes transmembrane region
Straight readthrough of C4 get tail piece added on and leads to secretory Ig
C4 has occult splice site, if it doesn’t read straight through, it spices to membrane anchor and forms transmembrane Ig

Question 21

Somatic hypermutation

Answer 21

Dependent on AID, not RAG
Expressed in activated B cells in germinal centres
Leads to mutations

Question 22

AID

Answer 22

Activation Induced Cytidine Deaminase

Converts cytosine to uridine resulting in introduction of mutations