W1L2 - B Cells

Question 1

5 Antibody Classes

Answer 1

IgM
- 10%
- primary response
- large, pentamer
IgG
- 75%
- only antibody that crosses the placenta
IgA
- 15%
- in mucous secretions and colostrum
IgE
- less than 1%
- immunity to parasites
- mediates allergic reactions
IgD
- less than 1%
- acts as antigen receptor on B cells

Question 2

5 Antibody Classes - Number of Antigen Binding Sites

Answer 2

IgM - 10
IgA - 4
IgG, E, D - 2

Question 3

What do Immunoglobulins act as?

Answer 3

Membrane bound antigen receptors on B cell surface = the B cell receptor (BCR)
Free antibodies in fluids = eliminate cells & pathogens expressing specific antigens

Question 4

Where do B Cells come from?

Answer 4

B cells development begins in the bone marrow
Driven by IL-7 produced by stromal cells
Cells activated by encountering specific antigen may secrete antibodies and/or
express increased levels of membrane antibodies
Activated B cells develop into long-lived plasma and memory cells
- persist in lymph nodes or return to the bone marrow

Question 5

B-1 and B-2 Cells

Answer 5

B-1 cells - fetal liver haematopoietic stem cells (HSCs)
- T cell independent antigens, make natural antibodies against polysaccharides
B-2 cells - bone marrow haematopoietic stem cells
- develop into marginal zone and follicular zone B cells in spleen

Question 6

Somatic Cell Recombination

Answer 6

Segments assembled into complete genes
- organisms do not inherit a single complete gene for antibody chains
- genetic information transmitted as multiple gene segments
Only two genes can do this: Immunoglobulins & T-cell receptor (TCR)
- two heavy and two light chain genes
- multiple variable and constant genes

Question 7

VDJ Recombination

Answer 7

Light chains have 300 V, 9 J and 1 C gene segments

Heavy chains have 11,000 V, 6 J, 5 C and 25 D segments

Question 8

Immunoglobulin Gene Segments

Answer 8

Light chains
- 3 gene segments
- variable, joining & constant 
Heavy chains
- 4 gene segments
- variable, diversity, joining, constant

Question 9

B Cell Activation

Answer 9

Human B cells express:
- TLR5 (bacterial flagellin)
- endosomal TLR7 (single-stranded RNA)
- TLR9 (unmethylated CpG-rich DNA)
These can recognise PAMPs and DAMPs given off by the pathogen
Activation of myeloid cells through TLR can also promote B cell activation indirectly
- dendritic cells -> helper T cell activation -> stimulate B cells
- myeloid cells secrete cytokines that can induce T-independent B cell responses

Question 10

Complement and B Cell Activation

Answer 10

B cells express a complex of the CR2 complement receptor, CD19 and CD81
Microbial antigens bind complement fragment C3d -> simultaneously engage CR2 and surface Ig (BCR)
Initiates signaling cascades from both BCR and CR2 complex – stronger response

Question 11

B Cell Activation and Antigen Presentation

Answer 11

Binding of antigen to surface Ig can lead to proliferation, upregulation of costimulatory molecules, antibody production
Can also lead to internalisation and antigen processing for presentation to CD4+ T cells

Question 12

What happens to B cells without T cell help?

Answer 12

B cells make IgM
Isotype switching is required to go from IgM to IgG
Isotype switching follows interaction between CD40 on B cell with CD40L on T cells in the presence of cytokines (IL-4, IL-13)
Interaction occurs in the germinal centre of lymph nodes

Question 13

B Cell Presentation to T Cell Steps

Answer 13

1. Dendritic cells present antigen to T helper cells
2. T helper cells recognise antigen -> activation -> express CD40L, secrete cytokines
3. CD40L on activated T helper cells binds to CD40 on B cells -> B cell proliferation and differentiation
4. Cytokines bind to cytokine receptors on B cells and also stimulate B cell responses

Question 14

Affinity Maturation

Answer 14

B cells must bind antigen on follicular dendritic cells to escape programmed cell death
B cells with highest affinity for antigen will win the race as antigen levels drop during an immune response
Affinity of antibodies increases as a response progresses

Question 15

Affinity Maturation in the Germinal Centre - Cellular Components

Answer 15

Dendritic cells stained in bright green in the light zone
B cells stained in dim green in the mantle zone
Replicating B cells stained in red in the dark zone
B cells with the highest affinity are selected to survive
- antibody secreting B cells
- or memory B cells

Question 16

Fc Receptors

Answer 16

Leukocytes express cell surface receptors that bind the Fc portion in the heavy chain of immunoglobulins
Fc receptors on neutrophils and macrophages mediate phagocytosis of opsonised particles and the activation of leukocytes to destroy phagocytosed particles

Question 17

Fc Receptors and B Cell Inactivation

Answer 17

B cell activation is down regulated by Fc receptors
Antigen-antibody complexes can simultaneously bind membrane Ig (BCR) and Fc receptor
Signalling by the BCR complex blocks B cell activation

Question 18

Fc Receptors - Other Functions

Answer 18

Fc receptors on NK cells directs the killing of antibody-coated target cells
Mast cells and basophils have Fc receptors for IgE
Epithelial cells express Fc receptors to mediate transepithelial antibody transport