Development of B lymphocytes

Question 1

Six stages of B cell Development?

Answer 1

1. Repertoire Assembly2. Negative Selection3. Positive Selection4. Searching for Infection5. Finding Infection6. Attacking Infection

Question 2

Negative selection prevents….Positive selection prevents….

Answer 2

Cells that bind selfCells that bind nothing

Question 3

Which selection takes place in the BM? the Lymphoid?

Answer 3

BM – Negative Selection2LN – Positive Selection

Question 4

Cell marker for Stem Cell? (common lymphoid progenitor)

Answer 4

CD34

Question 5

B Cell precursor marker? What is its significance?

Answer 5

IL-7R alphaDrive differentiation to Pro-B Cell

Question 6

5 Life Cycle Steps of B Cells associated with Stromal Cells

Answer 6

Lymphoid Progenitor CellEarly pro-B cellLate pro-B CellPre-B CellDissociation as an Immature B

Question 7

Lymphoid progenitor cell binds the stromal cell with…

Answer 7

CAMsVLA-4 —– VCAM-1

Question 8

Early pro-B binds to stromal cell with…

Answer 8

Kit —— SCF

Question 9

Significant component of Late pro-B cell phase?

Answer 9

IL-7 signaling from stromal to B cell Il-7 receptor (triggers differentiation)

Question 10

What’s going on between the Pre-B and the stromal?

Answer 10

Bound by CAMs, still getting IL-7

Question 11

What happens if V-DJ rearrangement of the H chain fails?

Answer 11

Try the 2nd chromosomeIf it still doesn’t work, apoptosis

Question 12

Describe the pre-B cell receptor

Answer 12

mu heavy chain + surrogate light chain

Question 13

What is a surrogate light chain?

Answer 13

Similar to LC, buts to HC to allow its expression because its not stable alone

Question 14

As far as Ig gene rearrangements go, whats happening in…Early Pro-BLate Pro-BPre-BImmature B

Answer 14

(H Chain) DJ Rearr(H Chain) V-DJ RearrL Chain RearrRearr ceases

Question 15

In one long obscene mess, describe the process of Ig gene rearrangement back ups.

Answer 15

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.

Question 16

Successful arrangement will have what influence on the other chromosome

Answer 16

Shut it down

Question 17

Value of allelic exclusion?

Answer 17

Ensures that the B lymphocyte expresses Ig molecules with only one specificity.This prevents accidental auto-reactive B cells

Question 18

How does allelic exclusion happen?

Answer 18

Successful rearrangement of the Ig gene segments of one allele shuts down the rearrangement process of the other.

Question 19

Why can’t the H chain rearrange?

Answer 19

Because of D genes btw V and JChanging it would delete the other alleles

Question 20

What happens if L-chain arrangement is unproductive?

Answer 20

Vk1 can be replaced w/ Vk2Works over and over till you run out of fragmentsDo the same with Js

Question 21

What happens in negative selection?

Answer 21

Self-reactive B cells are retained in marrow for rearrangement or apoptosis. Non-self-reactives move on to blood.

Question 22

Why isn’t the self-reactive B cell intrinsically fucked?

Answer 22

because the light chain can still rearrangeRearrange until successful, or runs out of Js and apoptosis

Question 23

What happens to B cels that bind soluble self-antigen?

Answer 23

Signaled to undergo anergySwitches to IgD and died shortly after

Question 24

Indicated by….Recurrent InfectionsNo Visible TonsilsLow-No Igs, No Mature BsBrother in same boatNormal WBC Profile

Answer 24

X Linked agammaglobulinemia

Question 25

Cause of X-linked agamaglobulinemia?

Answer 25

Defect in Bruton’s tyrosine kinase

Question 26

Genetic inheritance of X-linked agammaglob.

Answer 26

Recessive, X-linked

Question 27

Effect of X-linked agammaglob. on T cell levels?

Answer 27

None.

Question 28

Describe the path of B cells through the LN

Answer 28

Blood -> 2LN -> High Endo. Ven. -> Primary Fol -> Efferent Lymp. Vessel -> Thoracic Duct

Question 29

How do B cells get in the High Endo. Venules?

Answer 29

They express adhesin molecules that let Bs in

Question 30

Chemokine that attracts B cell to HEV?

Answer 30

CCL21

Question 31

Chemokines that attract B cell into lymph node?

Answer 31

CCL21. CCL19

Question 32

Chemokine that attracts B cell into primary follice?

Answer 32

CXCL13

Question 33

Maturation of B cells is driving by bonding with _____ cells and _______

Answer 33

Follicular Dendritic CellsCytokines

Question 34

What is BAFF?

Answer 34

B Cell Activating Factor

Question 35

Where does BAFF come from?

Answer 35

Goes from Folicular B Cells to BAFF receptor on B cell

Question 36

Role of BAFF in therapy

Answer 36

Ab against BAFF can be used to treat auto-immune disease

Question 37

What is lupus erthematosus?

Answer 37

Ab against connective tissue DNA

Question 38

What are B2 cells?

Answer 38

What we’re always talking about when we say B cells

Question 39

How are B1 cells special?

Answer 39

Produced in fetus – live in peritoneal/pleural cavitiesHigh Ig Production, Mostly IgMPolyreactive

Question 40

Why know B cell tumor origin?

Answer 40

Origin may be reflected in tumor attributesEsp. location

Question 41

Which B cell cancers are in BM and BloodWhat origin?

Answer 41

ALL (Lymphoid Progenitor)Pre-B cell leukemia (Pre-B)

Question 42

Which B cell cancer is almost only in BM?What origin?

Answer 42

Multiple Myeloma (Like Plasma Cell)

Question 43

Where is Hodgkin’s Lymphoma?

Answer 43

Primarily in LN