B-cell 3: Activation and Development

Question 1

B cell activation

Answer 1

• For most antigens, B-cells need help from T-cell to make antibodies (Tfh = T follicular helper cells; and TH2: t-helper cells). These are both CD4+ cells
• exception: some antigens can activate B-cells independent of t-cells (called thymus independent antigens). These tend to be highly repetitive structures like bacterial capsular polysaccharides

Question 2

T-helper cells

Answer 2

• antigen presenting cells (dendritic cells, macrophages, b-cells) are required to activate naive T-cells
• TH2 and Tfh cells that have been primed by the APC will seek B-cells that are presenting the same antigen

Question 3

Linked recognition

Answer 3

B-cell (which recognizes a certain antigen) will display some of that pathogens antigens on its surface through the MHC peptide molecule
- these then interact with the T-helper cell (t-cell receptor binds the MHC)

Linking of CD40 on the b-cell, with CD40 ligand on the T-helper cell.
- cytokine profile (IL-4, IL5, IL-6) allows t-cell to send a signal to the B-cell to start secreting antibodies

• B-cell proliferates
• B-cell differentiates to resting memory cells (which stay in bone marrow and lymphoid organs in case antigen is ever recognized again - will respond much faster) and plasma cells (which release antibodies)

Question 4

QUESTION

- what are the 3 requirements for a helper t-cell to activate a b cell to generate memory b cells or plasma cells?

Answer 4

1. T-cell receptor binding the MHC-peptide on the B-cell
2. CD40 ligand that binds CD40 on B-cell
3. Cytokines (IL-4,5,6)

Question 5

B-cell development

Answer 5

• complete most development in bone marrow, but can also develop in fetal liver and neonatal spleen
• B-cells are continually produced from the bone marrow (even in adults)

Question 6

Making the cut

Answer 6

• we need to get rid of any b-cells that make an antibody that can potentially recognize the hosts own self-proteins
• immature b-cells are tested for auto-reactivity before they leave the bone marrow (this is known as developing central tolerance)
• If B-cells “escape” - are found to be self-reactive in the periphery, they can still be removed (this is known as peripheral tolerance)

Question 7

B-cell and antibody development

Answer 7

B-cell development in bone marrow:

• VDJ recombination
• negative selection/central tolerance

Migration to peripheral lymphoid organs:
- stay here; if they encounter the antigen they will become activated (with the t-cells help)

Activated b-cells:

• give rise to memory b-cells or plasma cells
• antibody secretion in bone marrow and peripheral tissue

Question 8

Which B-cells are selected?

Answer 8

• once the antigen receptor has formed, rigorous testing occurs to determine if the b-cell will be deleted
• if the antigen receptor binds too strongly to self-antigens, it is DELETED
• if the antigen receptor binds weakly with self antigens and receives the right signal, KEEP

Question 9

Immature B-cells migrate to peripheral lymphoid tissue

Answer 9

• IgM expressing immature b-cells migrate to peripheral lymphoid tissue (undergo positive selection and further mature)
• immature b-cells must enter the follicle to survive
• continuous daily output of new B cells from bone marrow