Lecture 7.2

Question 1

B cell activation requires two _____, where from?

Answer 1

two signals

1. one from antigen binding to the B cell receptor
2. the other from Tcell (Th2 cell delivers second signal via CD40 ligand and cytokines)

Question 2

TH2 cells contain what important costimulatory molecule for B cell activation?

Answer 2

CD40L

binds to CD40 on B cell

Question 3

What determines whether a B cell becomes a memory or plasma cell?

Answer 3

**Cytokines - **released from TH2 cells

( = the third signal after antigen and CD40L)

Question 4

What is the first chain to undergo rearrangement in B cell development

Answer 4

the Heavy chain

Question 5

During IgH rearrangement, ____ are recombined first, followed by _____

Answer 5

D+J on both chromosomes

V-DJ on the first chromosome

Question 6

What happens if the V-DJ rearrangement on the first chromosome is unsuccessful?

Answer 6

V-DJ rearrangement on the second chromosome occurs.

If THAT one is unsuccessful, the cell is signaled to undergo apoptosis

Question 7

How many cells undergo apoptosis/survival during the transition from Late ProB cell to Pre-B cell?

Answer 7

50% apoptosis

50% signaled to go on to become PreB cell

Question 8

PreB cell contains ____ on its surface

How does this differ from a mature B cell?

Answer 8

PreBcell receptor

It has a surrogate light chain that is made of VpreB + λ5 instead of a normal light chain

Question 9

The surrogate light chain of a PreBcell receptor allows…

Answer 9

H chain expression on the surface of the PreB cell

Question 10

Which gene rearrangement occurs at the PreB cell stage?

Answer 10

L chain gene rearrangement

Question 11

Describe L chain rearrangement (fallback) steps

Answer 11

(Assuming each step is unsuccessful)

1. Rearrange K gene on 1st chromosome
2. Rearrange K gene on 2nd chromosome
3. Rearrange Lambda gene on 1st chromosome
4. Rearrange Lambda gene on 2nd chromosome
5. Apoptosis

Question 12

____ is the first L chain gene to rearrange, followed by ____

Answer 12

Kappa

Lambda

Question 13

__% of cells fail at L gene rearrangement, resulting in apoptosis

Answer 13

90%

Question 14

Successful rearrangement yields what two types of IgM

Answer 14

µ/K or µ/λ

Question 15

Allelic exclusion ensures that B cell…

Answer 15

expresses Ig molecules with only ONE specificity

Question 16

Mechanism of Allelic Exclusion

Answer 16

Successful gene rearrangement of one allele will shut down rearrangement of the other allele.

Question 17

______ rearrangements are possible at the Ig Light chain loci

Answer 17

Successive

(e.g. 2nd and 3rd VJ rearrangements)

Question 18

What are the two “checkpoints” of B cell development?

Answer 18

Selection of functional heavy chains and light chains

Question 19

The second step in B cell development involves negative selection of…

Answer 19

self-reactive B cells

Question 20

Explain negative selection of B cells in terms of where cells go in each situation

Answer 20

• 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

Question 21

Self reactive B cells continue to…

Answer 21

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

Question 22

In receptor editing, the B cell keeps rearranging its light chain genes until…

Answer 22

it either runs out of VDJ light chain segments or it successfully rearranges and leaves into the blood

Question 23

B cell that binds soluble antigen…

Answer 23

undergoes anergy

Question 24

What happens when a B cell becomes anergic?

Answer 24

It’s stimulated to produce only IgD (not IgM) and becomes unresponsive to antigens

It enters the bloodstream but dies quickly after

Question 25

X linked agammaglobulinemia is a ____, _____ disease, and is a defect of what gene

Answer 25

Recessive, X linked disease

defective Bruton’s Tyrosine Kinase (BTK)

Question 26

Effects of X linked agammaglobulinemia

Answer 26

Reduced Pre-B cells, no mature B cells

*Thymus is NORMAL (and Tcells normal)

Question 27

Treatment for X-linked agammaglobulinemia?

Answer 27

IVIG

antibiotics

Question 28

Why does the patient with X linked agammaglobulinemia NOT have tonsils?

Answer 28

No B cells = no follicles

(T cells still present)

Question 29

How are immature B cells attracted to lymph node?

Answer 29

CCL21 + CCL19

They enter via HEVs

Question 30

What happens once B cell enters the lymph node

Answer 30

They are attracted into the primary follicle by chemokine CXCL13

Question 31

What drives the maturation of immature B cells once they get into the lymph node?

Answer 31

They interact with follicular dendritic cells, which secrete BAFF

Question 32

Clinical significance of BAFF

Answer 32

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)

Question 33

5 Important differences between B-1 and B-2 cells

Answer 33

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!

Question 34

The IgM produced by B-1 cells are…

Answer 34

polyreactive

some have self recognition, but operate at low affinity so they are less likely to cause disease

Question 35

At any stage of B cell growth, it is possible to form…

Examples? (3)

Answer 35

neoplasms

Acute lymphoblastic leukemia = lymphoid progenitor

Hodgkin’s = Germinal center B cell

Multiple myeloma = Plasma cell