Immunological Memory B cells

Question 1

Immune system can trigger an Ab-driven response to any pathogen. This capacity is…

Answer 1

1. Pre-existing
2. Inducible
3. Amplifiable

Question 2

Trabeculae

Answer 2

Where immune cells develop from stem cells

Question 3

Yellow bone marrow

Answer 3

storage of fats in adipocytes

Question 4

What chain of Abs is the most diverse

Answer 4

CDR3

Question 5

Variable Chain of Ab

Answer 5

• Fv region

(new evidence: class switching may influence antigen binding/affinity/specificity of Fv domain)

Question 6

Constant regions of Ab play a role in…

Answer 6

• Ab class switching
• complement activation (CH2 domain)
• Fc receptor binding on APCs

Question 7

The initial Ab response

Answer 7

IgM

Question 8

Epitope

Answer 8

binding site on antigen for the Ab

*correct identification of epitopes important for vaccine, mAb development

Question 9

Paratope

Answer 9

Binding site on Ab for antigen

Question 10

CDRs

Answer 10

complement determining region - responsible for antigen/epitope recognition

*not all AA residues within CDR participate in antigen/epitope binding (~30%)

some parts of CDR involved in maintaining the structural conformation

Question 11

Structural Convergence

Answer 11

paratope structures (antigen-binding site) that recognise the same overlapping epitope can arise by either
- using the same or closely similar CDRH3 sequences
- using different VH,D,JV sequences
that produce the same epitope binding specificity

Question 12

Mechanisms for the generation of Ab diversity

Answer 12

1. Multiple germline V/D/J genes
2. VJ and VDJ recombinations
3. N-nucleotide addition
4. Recombinational inaccuracies
5. Somatic Hypermutation (SHM)
6. Class switching (CS)

Question 13

Enzyme involved in VDJ junctional diversity

Answer 13

TdT - terminal deoxynucleotide transferase

Question 14

Total no. of possible VDJ and JV combinations

Answer 14

~ 2x10^6

Question 15

Where do naive B cells migrate

Answer 15

secondary lymphoid organs

*most B cells never reach circulation due to failure of +ve/-ve selection

Question 16

Infinite Repertoire

Answer 16

estimates of Ab repertoire (10^15 - 10^18 members) - based on theoretical calculations

*not close to reality

Question 17

Why is the ‘infinite repertoire’ not close to reality

Answer 17

• only a small % of 10^9 produced daily are long-lived B cells
• most are removed in bone marrow as ‘self-reactive’
• if they fail to enter lymphoid follicles in lymph nodes or spleen (die by anergy/neglect)

Question 18

Current findings regarding B cell repertoires

Answer 18

• functional Ab rep composed of: naive, IgM, IgG/IgA memory B cells
• specificity of rep is much smaller
• different V gene segments used at different frequencies
• certain D genes more likely to recombine with specific J genes
• SMH is biased (mutations occur more often in hotspots in heavy chain genes)

Question 19

CDRH3

Answer 19

• the region that adds and deletes NTs to the V-D junction on the heavy chain
• has great variation in length - plays role in antigen recognition
• if antigen recognition is driven by CDRH3 sequences, memory convergence in secondary and tertiary responses should be seen where hypermutation has occurred - this is seen

Question 20

Before leaving the bone marrow (to LN & spleen) naive B cells

Answer 20

• successfully recombined Ab genes and produced a functional cell surface Ab, BCR
• been selected to ensure they don’t react with self-antigens i.e. not autoreactive
• express both IgM and IgD on their surface

Question 21

Serum 1/2 life for IgM vs IgG

Answer 21

IgM: 5 days
IgG: 8-23 days

Question 22

Least variable region of Ab

Answer 22

Framework Regions