B-cells

Question 1

What are the stages of b-cell development?

Answer 1

Pluripotent Heamtepoetic Stem Cell, Early Pro-B-cell, late Pro-B-cell, Large Pre-B-cell, Small Pre-B-cell, Immature B-cell, Translation B-cell, Mature or follicular B-cell, Plama Cell (with ab)
Memory B-cell (without ab) - Plasma cell

Question 2

What are B-cells Derived from ?

Answer 2

Common lymphoid Progenitors

Question 3

What are B-cell defined by ?

Answer 3

The Ig

Question 4

What are the 5 surface Ig on B-cells?

Answer 4

IgA, IgG, IgM, IgE, IgD

Question 5

Where are antibodies Generally secreted from?

Answer 5

The Plasma cells and some B-cells

Question 6

Where does B-cell rearrangement take place ?

Answer 6

Germline Ig Gene

Question 7

\What are the 4 regions of Germline Ig?

Answer 7

Variable (V) Diverse (D), Joining (J), Constant (C)

Question 8

What is non-homologous recombination ?

Answer 8

B-cell heavy chain re-arranged, starting with D,J arrangement followed by V-DJ re-arrangement followed by light chain arrangement in the form of Landa of Kappa chains

Question 9

What is Allelic exclusion?

What are the results of allelic exclusion?

Answer 9

Ligation of Pre-B-cell receptor, and suppression of H chain re-arrangement.
Ensure only one 1 Ab is present on B-Cell
Ensures only the pre-B-cells are expanded within the VhDhJh joins
Triggers entry of Pre-B-cell into cell cycle.

Question 10

What is clonal deletion?

Answer 10

Immature B-cells recognise multivalent self Antigens which generates high levels of signal. This results cross linking of Surface IgMs and apoptosis.

Question 11

What is Anergy?

Answer 11

Immature B-cells recognise soluble self antigen with no cross-linking
Surface IgM levels down regulated and IgD remains as normal. This results in a mature B-Cell unresponsive to Ag

Question 12

What is receptor editing?

Answer 12

Receptor editing is where Re-combination genes are re-activated (switched off in pre-B-cell).
This results in new surface receptor synthesis and if the b-cell does not recognise self antigen, it can migrate to the lymph node as a mature B-cell.

Question 13

Name 2 properties of B-cell receptors

Answer 13

1- Oligomeric 2- auto-inhibited

Question 14

What Happens when antigen (ag) bind to B-Cell Receptors (BCR)?

Answer 14

1-Ag binding to BCR first induces B-cell clusters to open
2-This leads to inhibition of phosphates activity are recruitment of Sre family kinases (Lyn, Fyn, BLK)
3- This leads to phosphorylation of ITAMS via Ig alpha/beta
4- Phosphorylation of ITAMS recruits Syk, facilitating further Ig alpha/beta phosphorylation
5- This leads gto downstream signalling and B-cell proliferation and differentiation
6- This allows BCR to internalise Ag and process it for presentation to CD4+ T-cells through MHC II expression

Question 15

What are the Sre Family kinases recruited to B-cells on phosphates inhibition

Answer 15

Lyn, Fyn, BLK

Question 16

Why do B-cells have Co-receptor complexes and can you name an example of one?

Answer 16

B-cells have co-receptor complexes to enhance the activation signal
CR2 is an example of a b-cell co-receptor

Question 17

What does the B-cell co-receptor CR2 do?

Answer 17

CR2 binds to complement fragment C3D and can magnify CD3 by 4x magnitude. This means at low Ag dose, complement signal comes together to enhance and activate B-cell signal

Question 18

What happens when Ag binds/crosslinks surface Ig and activates the B-cell (signal 1)?

Answer 18

1 - B-cell internalises Ag and expresses CD40
2- Ag is processed by B-cell and expressed on MHC II
3- T helper cells bind to b-cell via CD40 through cytokine signals and provide signal 2

Question 19

What are the outcomes of Ag binding?

Answer 19

Weak signal (signal 1 only), mean B-cells are prone to apoptosis 
B-cell require signal 1 and 2, once this happens they can up-regulate Bcl-X in the B-cell and prevent apoptosis

Question 20

Which cytokines are produced from signal 2 and what effect does this have on the B-cell?

Answer 20

IL-4, IL-5, IL-6, IFN gamma, TGF-beta
This activates B-cells and makes B-cells begin somatic hypermutation of the Ig CDR encoding protein at the Ig genes and also then form a germinal centre

Question 21

1) What is the purpose of the Germinal Centre?

2) What cell must B-cell maturation occur in the presence of?

Answer 21

1)Allows a process of b-cell maturation where they switch low affinity IgM phenotypes to high affinity IgG types. this allows for better recognition and binding capabilities.
Also develop memory B-cells in GC
2)T-cells

Question 22

1) What are the roles of T-cells in the germinal centre?
2) What are the roles of follicle DCs in the germinal centre?
3) Why do B-cells need to test binding capabilities?

Answer 22

1) T-cells in the germinal centre produce cytokine (eg IL-21)
2) Express Ag to B-cells and allow them to test their binding capabilities.
3) B-cells slowly change their V region

Question 23

What is affinity maturation?

Answer 23

Where B-cells improve their binding capabilites via interactions with DCs and T-cells

Question 24

What is a B-1 B-cell?

Answer 24

Subunit of B-cells that produce IgM and express CD5
They play important role in innate immunity
IgM is a natural antibody
They are non-bone marrow derived B-cells stimulated by antigens containing multivalent epitopes

Question 25

What is a TI-2 B-cell (or Type 2 Independant B-cell) ?

Answer 25

look it up