Lecture 7.2 Flashcards
B cell activation requires two _____, where from?
two signals
- one from antigen binding to the B cell receptor
- the other from Tcell (Th2 cell delivers second signal via CD40 ligand and cytokines)
TH2 cells contain what important costimulatory molecule for B cell activation?
CD40L
binds to CD40 on B cell
What determines whether a B cell becomes a memory or plasma cell?
**Cytokines - **released from TH2 cells
( = the third signal after antigen and CD40L)
What is the first chain to undergo rearrangement in B cell development
the Heavy chain
During IgH rearrangement, ____ are recombined first, followed by _____
D+J on both chromosomes
V-DJ on the first chromosome
What happens if the V-DJ rearrangement on the first chromosome is unsuccessful?
V-DJ rearrangement on the second chromosome occurs.
If THAT one is unsuccessful, the cell is signaled to undergo apoptosis
How many cells undergo apoptosis/survival during the transition from Late ProB cell to Pre-B cell?
50% apoptosis
50% signaled to go on to become PreB cell
PreB cell contains ____ on its surface
How does this differ from a mature B cell?
PreBcell receptor
It has a surrogate light chain that is made of VpreB + λ5 instead of a normal light chain
The surrogate light chain of a PreBcell receptor allows…
H chain expression on the surface of the PreB cell
Which gene rearrangement occurs at the PreB cell stage?
L chain gene rearrangement
Describe L chain rearrangement (fallback) steps
(Assuming each step is unsuccessful)
- Rearrange K gene on 1st chromosome
- Rearrange K gene on 2nd chromosome
- Rearrange Lambda gene on 1st chromosome
- Rearrange Lambda gene on 2nd chromosome
- Apoptosis
____ is the first L chain gene to rearrange, followed by ____
Kappa
Lambda
__% of cells fail at L gene rearrangement, resulting in apoptosis
90%
Successful rearrangement yields what two types of IgM
µ/K or µ/λ
Allelic exclusion ensures that B cell…
expresses Ig molecules with only ONE specificity
Mechanism of Allelic Exclusion
Successful gene rearrangement of one allele will shut down rearrangement of the other allele.
______ rearrangements are possible at the Ig Light chain loci
Successive
(e.g. 2nd and 3rd VJ rearrangements)
What are the two “checkpoints” of B cell development?
Selection of functional heavy chains and light chains
The second step in B cell development involves negative selection of…
self-reactive B cells
Explain negative selection of B cells in terms of where cells go in each situation
- If the immature B cell doesn’t react* with bone marrow cell, it moves to the blood and expresses both IgD and IgM
- If it does react* with the bone marrow cells, it stays put
Self reactive B cells continue to…
make a new light chain (and thus change specificity), and continue rearrangement of VJ segments.
It leaves once it comes up with one that isn’t self reactive
In receptor editing, the B cell keeps rearranging its light chain genes until…
it either runs out of VDJ light chain segments or it successfully rearranges and leaves into the blood
B cell that binds soluble antigen…
undergoes anergy
What happens when a B cell becomes anergic?
It’s stimulated to produce only IgD (not IgM) and becomes unresponsive to antigens
It enters the bloodstream but dies quickly after
X linked agammaglobulinemia is a ____, _____ disease, and is a defect of what gene
Recessive, X linked disease
defective Bruton’s Tyrosine Kinase (BTK)
Effects of X linked agammaglobulinemia
Reduced Pre-B cells, no mature B cells
*Thymus is NORMAL (and Tcells normal)
Treatment for X-linked agammaglobulinemia?
IVIG
antibiotics
Why does the patient with X linked agammaglobulinemia NOT have tonsils?
No B cells = no follicles
(T cells still present)
How are immature B cells attracted to lymph node?
CCL21 + CCL19
They enter via HEVs
What happens once B cell enters the lymph node
They are attracted into the primary follicle by chemokine CXCL13
What drives the maturation of immature B cells once they get into the lymph node?
They interact with follicular dendritic cells, which secrete BAFF
Clinical significance of BAFF
Anti-BAFF MAb’s are used to treat SLE
(SLE = B cells make antibodies against histones, and form immune complexes that deposit in the kidney and skin)
5 Important differences between B-1 and B-2 cells
B1 are the weird ones, B2 are normal.
B1 cells:
- Produce more IgM > IgG
- fetal
- have low diversity (N and V regions)
- do NOT need T-cell help
- DONT undergo somatic hypermutation!
The IgM produced by B-1 cells are…
polyreactive
some have self recognition, but operate at low affinity so they are less likely to cause disease
At any stage of B cell growth, it is possible to form…
Examples? (3)
neoplasms
Acute lymphoblastic leukemia = lymphoid progenitor
Hodgkin’s = Germinal center B cell
Multiple myeloma = Plasma cell
