B cell maturation & development

Question 1

what is the positive signal for lymphoid-myeloid primed multipotent progenitors (LMPPs) to transition to Common lymphoid progenitors (CLP)?

Answer 1

LMPPs interact with FLT3 ligand signalling them to become CLP

Question 2

what happens in early pro-B cells? what is the positive signal to progress to late pro-B cells?

Answer 2

DJ rearrangement of the heavy chain - successful rearrangement (eg. no frame shifts) is the positive signal to progress

Question 3

what happens in late pro-B cells? what is the positive signal to progress to large pre-B cells?

Answer 3

V-DJ rearrangement of the heavy chain - successful rearrangement is the positive signal to progress

Question 4

what happens in large pre-B cells? what is the positive signal to progress to small pre-B cells?

Answer 4

Two main things happen in this stage.
1. surrogate light chain binds previously formed VDJ heavy chain
2. cross-linking of pre-BCRs formed > ITAMs > Btk

both of these are the positive signals to progress

Question 5

what happens in small pre-b cells? what is the positive signal to progress to immature/naive b cells?

Answer 5

VJ rearrangement of the light chain occurs - positive signal is successful joining of heavy and light chains

Question 6

what must happen before naive B cells can leave the bone marrow?

Answer 6

central tolerance @ BONE MARROW of BCR has 4 outcomes.

no self reaction = move to spleen

reacts to multivalent self molecule = apoptosis or receptor editing can save it

reacts to soluble self molecule = anergic

reacts to low-affinity non-crosslinking self molecule = mature b cell (only as issue if lots of these)

Question 7

what are the steps of b cell maturation in the spleen?

Answer 7

naive b cells enter follicles as transitional b cells (don’t enter follicle = die of neglect)

FDCs present BAFF to them which is an ESSENTIAL positive signal for them to either become follicular or marginal B cells

*also needs weak BCR interactions

Question 8

where does peripheral tolerance occur? how does it differ to central tolerance?

Answer 8

less forgiving as B cells are relatively mature from follicle interactions

no self reaction = mature B cell

reacts to multivalent self molecule = apoptosis

reacts to soluble self molecule = apoptosis

reacts to low-affinity non-crosslinking self molecule = mature b cell (only as issue if lots of these)