Development of B lymphocytes Flashcards
Six stages of B cell Development?
- Repertoire Assembly2. Negative Selection3. Positive Selection4. Searching for Infection5. Finding Infection6. Attacking Infection
Negative selection prevents….Positive selection prevents….
Cells that bind selfCells that bind nothing
Which selection takes place in the BM? the Lymphoid?
BM – Negative Selection2LN – Positive Selection
Cell marker for Stem Cell? (common lymphoid progenitor)
CD34
B Cell precursor marker? What is its significance?
IL-7R alphaDrive differentiation to Pro-B Cell
5 Life Cycle Steps of B Cells associated with Stromal Cells
Lymphoid Progenitor CellEarly pro-B cellLate pro-B CellPre-B CellDissociation as an Immature B
Lymphoid progenitor cell binds the stromal cell with…
CAMsVLA-4 —– VCAM-1
Early pro-B binds to stromal cell with…
Kit —— SCF
Significant component of Late pro-B cell phase?
IL-7 signaling from stromal to B cell Il-7 receptor (triggers differentiation)
What’s going on between the Pre-B and the stromal?
Bound by CAMs, still getting IL-7
What happens if V-DJ rearrangement of the H chain fails?
Try the 2nd chromosomeIf it still doesn’t work, apoptosis
Describe the pre-B cell receptor
mu heavy chain + surrogate light chain
What is a surrogate light chain?
Similar to LC, buts to HC to allow its expression because its not stable alone
As far as Ig gene rearrangements go, whats happening in…Early Pro-BLate Pro-BPre-BImmature B
(H Chain) DJ Rearr(H Chain) V-DJ RearrL Chain RearrRearr ceases
In one long obscene mess, describe the process of Ig gene rearrangement back ups.
If V-DJ doesn’t work, you get a 2nd try. If neither works, apoptosis. If kappa1 doesn’t work, try kap2, if kap2 doesn’t work, try lamb. 1. If Lambda 1 doesn’t work, try lamb. 2. If none of the 4 work, apoptosis.
Successful arrangement will have what influence on the other chromosome
Shut it down
Value of allelic exclusion?
Ensures that the B lymphocyte expresses Ig molecules with only one specificity.This prevents accidental auto-reactive B cells
How does allelic exclusion happen?
Successful rearrangement of the Ig gene segments of one allele shuts down the rearrangement process of the other.
Why can’t the H chain rearrange?
Because of D genes btw V and JChanging it would delete the other alleles
What happens if L-chain arrangement is unproductive?
Vk1 can be replaced w/ Vk2Works over and over till you run out of fragmentsDo the same with Js
What happens in negative selection?
Self-reactive B cells are retained in marrow for rearrangement or apoptosis. Non-self-reactives move on to blood.
Why isn’t the self-reactive B cell intrinsically fucked?
because the light chain can still rearrangeRearrange until successful, or runs out of Js and apoptosis
What happens to B cels that bind soluble self-antigen?
Signaled to undergo anergySwitches to IgD and died shortly after
Indicated by….Recurrent InfectionsNo Visible TonsilsLow-No Igs, No Mature BsBrother in same boatNormal WBC Profile
X Linked agammaglobulinemia
