Lecture 7: B-Cell Development and Antibody Maturation

Question 1

B cells develop in the __________ and mature in the _______ and ____________.

Answer 1

Bone Marrow

Spleen and Lymph nodes

Question 2

Explain how antibody diversity is achieved:

Answer 2

VDJ rearrangement

Question 3

What is somatic hypermutation?

Answer 3

A process that introduces point mutations into the rearranged V region genes of activated B cells which creates further diversity and specificity for ag

Question 4

What are the components of the Light and Heavy chain genes:

Answer 4

Light Chain:
- V and J regions
Heavy Chain:
- V, D and J regions

Question 5

Describe B-Cell receptor development:

Answer 5

Phase 1: Heavy Chain rearrangement
- D to J rearrangement first
- Then V-DJ
Phase 2: Light Chain rearrangement
- V to J rearrangement

Question 6

What is allelic exclusion?

Answer 6

A process by which only one allele of a gene is expressed while the other allele is silenced, it’s important for establishing specificity. Can occur at pre-BCR and BCR stages

Question 7

Explain Receptor editing:

Answer 7

• B cell has receptors strongly cross-linked by multivalent self ag => development is arrested
• Decreases expression of IgM and does not turn of RAG genes = light chain can rearrange again
• Usually leads to a productive receptor

Question 8

What are the two ways that B cells can be activated?

Answer 8

T-independent

T-dependent

Question 9

Explain T-independent activation and what it responds to:

Answer 9

• T-independent ag include LPS and polysaccharide capsules
• They have repetitive epitopes which allows cross-linkage of multiple BCRs
• ag binds to BCR, requires co-stim via TLRs and PAMPs or the C’ system
• Short lived response that doesn’t make memory cells

Question 10

Explain T-dependent activation and what it responds to:

Answer 10

• Responds to free protein ag or ag on an intact pathogen
• Ag are internalized when they bind to BCRs and get processed and presented on MHC2
• CD4s that recognize the same epitope with interact via the MHC (linked recognition) and stimulate the B cell

Question 11

How does class switching occur?

Answer 11

μ chain heavy chain constant regions are replaced by heavy chain C regions of another isotype, does not effect specificity

Question 12

How do B and Helper T cells come into contact in T-dependent activation?

Answer 12

If a B cell encounters it’s ag via folicular dendritic cells or subcapsular macrophages then it migrates to the T-cell rich area where it can contact CD4s

Question 13

Activated B cells form ______________ in the lymphoid follicles

Answer 13

Germinal centres

Question 14

Circulating naive B cells enter the lymph node via the ______ and home to the _________________. If they do not encounter their ag they leave via the ___________.

Answer 14

HEV
Primary Lymphoid Follicle
Efferent Lymphatics

Question 15

What do B cells do when activated?

Answer 15

• Move to the T cell rich area to get T-cell help
  or
• For a primary focus in the medullary cods
  or
• Move back into the follicle and form a germinal centre

Question 16

Where does somatic hypermutation occur?

Answer 16

In the Dark zone of the germinal centre

Question 17

Where does class switching occur?

Answer 17

In the Light zone of the germinal centre