B Cells: Development Flashcards
phase 1
generation of diverse and clonally expressed B-cell receptors in the bone marrow
phase 2
alteration, elimination or inactivation of B-cell receptors that bind to components of human body.
*negative selection
phase 3
promotion of a fraction of immature B cells to become mature B cells in the secondary lymphoid tissues
* positive selection
phase 4
recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues
phase 5
activation and clonal expansion of B cells by pathogen-derived antigens in the secondary lymphoid tissues
phase 6
differentiation to antibody-secreting plasma cells and memory B cells in secondary lymphoid tissue
are B cells stockpiled?
NO, they are constantly replaced
30 billion/day
half life is 50-100 days thus population is winnowed down
when does the D-J of the heavy chain rearrange?
Early pro-B cell
when dos the DJ-V of the heavy chain rearrange?
Late pro-B cell
what is the first checkpoint of B cell development?
after the heavy chain has rearranged
Late pro-B cell
when is the heavy chain made?
Large pre-B cell
when does the V-J rearrange of the light chain?
small pre-B cell
when is the second checkpoint of B cell maturation?
after the light chain has rearranged
small pre-B cell
What is expressed on the surface of an immature B cell?
IgM
what is the order of B cell development?
early pro, late pro, large pre, small pre, immature
Stromal cells interact and drive B cell development how?
- express adhesion molecules and growth factors
- B cell receptor expression changes with progression through development
- Pro-B cells are programmed to die in the absence of survival signals
Does the D-J rearrange happen on both chromosomes?
yes
*early pro-B cell
If the V-DJ doesn’t happen on one chromosome what happens?
it gets another chance on the other chromosome, if this also fails then the cell dies. Junctional diversity errors result in non successful formation of heavy chain
*Late pro-B cell
Early Pro-B cell
RAG proteins activated
heavy chain D and J segments joined
occurs on both chromosomes
Late-Pro-B cell
heavy V and DJ segments joined
occurs sequentially on chromosomes
two chances for RAR
*first checkpoint happens now for functional heavy chain
what is the pre B cell receptor?
causes transition form Pro to Pre B cell
it is expressed in the ER
**surrogate light chain expressed and ensures a light chain can bind
Ig alpha and beta expressed(allows signaling)
Ig alpha and beta
checkpoint clearance
turns of RAG proteins
initiates cell division
-Allelic exclusion(heavy chain only from one chromosome)
why is allelic exclusion important?
ensures specificity of the heavy chain not allowing for a mixture of heavy chain production
Once the late pro-B cell has made it through the checkpoint and transitions into a Large -Pre-B cell what happens?
cell division:
100 small pre-B cells
RAG genes activated
unique recombination per cell(light chain)