Development of B Lymphocytes Flashcards
Six stages of B cell Development?
- Repertoire Assembly
- Negative Selection
- Positive Selection
- Searching for Infection
- Finding Infection
- Attacking Infection
Negative selection prevents….
Positive selection prevents….
Cells that bind self
Cells that bind nothing
Which selection takes place in the BM? the Lymphoid?
BM – Negative Selection
2LN – Positive Selection
Cell marker for Stem Cell? (common lymphoid progenitor)
CD34
B Cell precursor marker? What is its significance?
IL-7R alpha
Drive differentiation to Pro-B Cell
5 Life Cycle Steps of B Cells associated with Stromal Cells
Lymphoid Progenitor Cell Early pro-B cell Late pro-B Cell Pre-B Cell Dissociation as an Immature B
Lymphoid progenitor cell binds the stromal cell with…
CAMs
VLA-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 chromosome
If 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-B Late Pro-B Pre-B Immature B
(H Chain) DJ Rearr
(H Chain) V-DJ Rearr
L Chain Rearr
Rearr 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 J
Changing it would delete the other alleles
What happens if L-chain arrangement is unproductive?
Vk1 can be replaced w/ Vk2
Works over and over till you run out of fragments
Do 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 rearrange
Rearrange until successful, or runs out of Js and apoptosis
What happens to B cels that bind soluble self-antigen?
Signaled to undergo anergy
Switches to IgD and died shortly after
Indicated by.... Recurrent Infections No Visible Tonsils Low-No Igs, No Mature Bs Brother in same boat Normal WBC Profile
X Linked agammaglobulinemia
Cause of X-linked agamaglobulinemia?
Defect in Bruton’s tyrosine kinase
Genetic inheritance of X-linked agammaglob.
Recessive, X-linked
Effect of X-linked agammaglob. on T cell levels?
None.
Describe the path of B cells through the LN
Blood -> 2LN -> High Endo. Ven. -> Primary Fol -> Efferent Lymp. Vessel -> Thoracic Duct
How do B cells get in the High Endo. Venules?
They express adhesin molecules that let Bs in
Chemokine that attracts B cell to HEV?
CCL21
Chemokines that attract B cell into lymph node?
CCL21. CCL19
Chemokine that attracts B cell into primary follice?
CXCL13
Maturation of B cells is driving by bonding with _____ cells and _______
Follicular Dendritic Cells
Cytokines
What is BAFF?
B Cell Activating Factor
Where does BAFF come from?
Goes from Folicular B Cells to BAFF receptor on B cell
Role of BAFF in therapy
Ab against BAFF can be used to treat auto-immune disease
What is lupus erthematosus?
Ab against connective tissue DNA
What are B2 cells?
What we’re always talking about when we say B cells
How are B1 cells special?
Produced in fetus – live in peritoneal/pleural cavities
High Ig Production, Mostly IgM
Polyreactive
Why know B cell tumor origin?
Origin may be reflected in tumor attributes
Esp. location
Which B cell cancers are in BM and Blood
What origin?
ALL (Lymphoid Progenitor)
Pre-B cell leukemia (Pre-B)
Which B cell cancer is almost only in BM?
What origin?
Multiple Myeloma (Like Plasma Cell)
Where is Hodgkin’s Lymphoma?
Primarily in LN
