B cell generation Flashcards
what is the steps to form a immature B cell starting with a hematopoietic stem cell?
HSC –> multi-potent progenitor –> common lymphoid progenitor –> Early Pro-B cell –> late pro B-cell –> pre B cell –> immature B cell
what are bone marrow stromal cells?
important cells in bone marrow for early B cell development.
B cell development: multi-potent –> common lymphoid
- the multi-potent cell secretes FLT 3 which binds stromal cell FLT 3 receptor.
- Stromal cells release CXCL12 which is a chemokine that keeps the MPC close to the bone marrow
- complete FLT signalling turns MPC into CLP
B cell development: CLP –> Early pro B cell
- Once CLP is made it expresses IL-7 cytokine receptor (IL-7 facilitates the progression of the cell)
- the CLP also produces CAM proteins (cell adhesion molecules) and VLA molecules. These act ac anchors.
B cell development: Early pro B cell –> late pro B
- the expression of CAMPs and binding of IL-7 causes the CLP to become an early pro B cell.
- The early pro B cell produces KIT (tyrosine kinase) and SCF (stem cell factor) which binds the cell to the bone marrow
- this KIT protein causes early B –> late B
B cell development: late pro-B cell –> pre B cell
- IL-7 binding causes the late pro B cell to now become a pre B cell
- now the cell stops its production of KIT and begins its production of H chain antibody. It also makes a surrogate light chain
B cell development: pre B cel –> immature B cell
light chain is expressed and real MB antibody is made
Pre B cells have two stages
- Large pre B cell
- Small pre B cell
explain each
- the large pre B cell is the cell that expresses the heavy chain of the antibody and the surrogate light chain
- then a signal molecule (Ig alpha / beta dimer) will signal the cell to stop producing heavy chain once it recognizes heavy chain on the cell surface.
- Now H chain production is shut down and light chain production begins –> now a small pre B cell
- when a real antibody (IgM) is made = immature B cell.
true or false, the large Pre - B cell receptor (the heavy chain on cell surface) in conjunction with the Ig alpha / beta dimer 1. stops H chain expression 2. signals light chain expression
true
What is VpreB and lambda 5?
the surrogate light chain
VpreB = variable
lambda 5 = conserved
when is the Ig alpha/beta dimer expressed and when does it last till?
it begins expression in the pro B cell stage and stops only after the mature B cell stage.
it acts to transduce a signal to the cell when the H chain has properly been made and the light chain needs to start expression (beginning of small pre B cell stage) ell AND when a naive mature B cell has interacted with an antigen.
when does an immature B cell become mature?
typically it migrates through secondary lymphoid tissue where it acquires IgD expression.
what is allelic exclusion?
the mechanism responsible for mature B cells recognizing a single antigen
in terms of genes, what occurs at each step?
Early Pro B cell
Late Pro B cell
Pre B cell
immature B cell
Early Pro B cell –> H chain rearrangement (D-J)
Late Pro B cell –> H chain rearrangement (V-DJ)
Pre B cell –> L chain rearrangement (only after alpha beta dimer tells the cell H chain is complete)
immature B cell –> rearrangements cease.
explain the process of allelic exclusion from Early Pro B cell Late Pro B cell Pre B cell immature B cell
Early Pro B cell –> at this stage D and J join together in the first somatic recombination step on BOTH CHROMOSOMES / ALLELES
Late Pro B cell –> V-DJ recombination occurs on X1. If this fails it occurs on X2. If this fails it dies.
Pre B cell --> if either cell makes a proper V-DJ step then a Pre B cell is formed. Now light chain rearrangement occurs. (as these rearrangements are occurring, the large pre B cell is expressing the recently rearranged H chain) 1. X1 kappa rearrangement 2. X2 kappa rearrangement 3. X1 lambda "" 4. X2 lambda one and two will make a kappa IgM three and four make a Lambda IgM if none work the cell dies.
immature B cell
