B-cells Flashcards
What are the stages of b-cell development?
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
What are B-cells Derived from ?
Common lymphoid Progenitors
What are B-cell defined by ?
The Ig
What are the 5 surface Ig on B-cells?
IgA, IgG, IgM, IgE, IgD
Where are antibodies Generally secreted from?
The Plasma cells and some B-cells
Where does B-cell rearrangement take place ?
Germline Ig Gene
\What are the 4 regions of Germline Ig?
Variable (V) Diverse (D), Joining (J), Constant (C)
What is non-homologous recombination ?
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
What is Allelic exclusion?
What are the results of allelic exclusion?
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.
What is clonal deletion?
Immature B-cells recognise multivalent self Antigens which generates high levels of signal. This results cross linking of Surface IgMs and apoptosis.
What is Anergy?
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
What is receptor editing?
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.
Name 2 properties of B-cell receptors
1- Oligomeric 2- auto-inhibited
What Happens when antigen (ag) bind to B-Cell Receptors (BCR)?
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
What are the Sre Family kinases recruited to B-cells on phosphates inhibition
Lyn, Fyn, BLK
Why do B-cells have Co-receptor complexes and can you name an example of one?
B-cells have co-receptor complexes to enhance the activation signal
CR2 is an example of a b-cell co-receptor
What does the B-cell co-receptor CR2 do?
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
What happens when Ag binds/crosslinks surface Ig and activates the B-cell (signal 1)?
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
What are the outcomes of Ag binding?
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
Which cytokines are produced from signal 2 and what effect does this have on the B-cell?
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
1) What is the purpose of the Germinal Centre?
2) What cell must B-cell maturation occur in the presence of?
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
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?
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
What is affinity maturation?
Where B-cells improve their binding capabilites via interactions with DCs and T-cells
What is a B-1 B-cell?
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
What is a TI-2 B-cell (or Type 2 Independant B-cell) ?
look it up
