What is the general steps of B cell development (7)
1.Hematopoietic stem cell
2.Common lymphoid progenitor
3.Progenitor B-cell
4. Pre B-cell
5. Immature B-cell
6.Mature (naïve) B-cell
7. Activated B-cell – peripheral lymphoid organ
Antibody secreting plasma cell
Memory B-cell
In what stage does b cell receptor rearrangement occur
Pro B cell stage
How are b cell receptors set up
made of 2 identical antigen binding sites
2 light(a) and 2 heavy(b) chains
What are the 2 states the b cell receptor can be in
expressed on cell surface
or recreated (antibody)
What chain is generated first in the pro b cell stage
Heavy chain
How is the B chain (variable region) created
VDJ recombinase catalyzes D genes (12) combining with J (23) genes and then it recombines with the V section
How is the heavy chain tested (and stage of development this is done)
Pre B stage the heavy chain is tested on cell surface using surrogate light chain and must be able to interact with IgB and igA
At what stage does the light chain start developing
Pre b stage
What are the two light chain genes to choose from and chromosome they on
Kappa light chain (chromosome 2)
Lamda light chain (chromosome 22)
will have 2 of one or the other
How does recombination occur on the light chain
Only has V and J gene segments that recombine (with 12/23 rule)
if the pre b cell has good heavy and light chains what will happen and what stage will it move to
Proliferate many times
-move from large to small pre b cell stage
What configuration will b cells have on its surface when its immature
iGm receptor
What happens in positive selection of b cells
b cells are positively selected when signalling occurs through the pre b receptor (heavy chain testing)
what happens in negative selection of immature b cells
involves interactions between the default IgM receptor and self antigens
what are the options for negative selection
- no rxn to self- mature
- rxn to multivalent self molecules resulting in clonal deletion/receptor editing
- rxn to self molecules (non cross linking) becoming anergia
in what area of the lymph node is the b cell activated
germinal center in primary lymphoid follicle
Overall steps on how b cell are activated
B cell binds to antigen that it is specific to and is internalized by b cell and processed on MHC2 which attached to helper t cell (t cell provides 3 signals)
What are the 3 signals provided to the b cell by the t cell to activate it
- Th1/2 binds to MCH + antigen
- CD40(on b) binds to CD40L
- Th1 releases IFN + Th2 releases IL4
Once b cells recieve all 3 signals they may differentiate into (2)
- Plasma cells (antibody secreting cells)
2. Memory b cells
what is somatic hypermutation and when does it happen
As b cell proliferates VDJ gene segments can undergo random mutation which could change binding strength to antigens
(ONLY HAPPENS IN B CELLS)
What is isotype switching and when does it occur
When b cells are proliferating after activation
Heavy chain can express different constant genes which determine antibody effector function!
What is responsible for isotype switching + enzyme
specific cytokines
enzyme: activation induced cytidine deaminase
What are follicular helper t cells important for (4) + effector cytokine responsible
interact with activated b cells and:
- form germinal centers
- Somatic hypermutation
- b cell survival
- class switching
-Il21
Generally how do memory b cells work
when a memory b cells bar binds to its epitope it may differentiate into antibody secreting plasma cells
