Development of B Lymphocytes Flashcards

1
Q

Six stages of B cell Development?

A
  1. Repertoire Assembly
  2. Negative Selection
  3. Positive Selection
  4. Searching for Infection
  5. Finding Infection
  6. Attacking Infection
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2
Q

Negative selection prevents….

Positive selection prevents….

A

Cells that bind self

Cells that bind nothing

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3
Q

Which selection takes place in the BM? the Lymphoid?

A

BM – Negative Selection

2LN – Positive Selection

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4
Q

Cell marker for Stem Cell? (common lymphoid progenitor)

A

CD34

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5
Q

B Cell precursor marker? What is its significance?

A

IL-7R alpha

Drive differentiation to Pro-B Cell

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6
Q

5 Life Cycle Steps of B Cells associated with Stromal Cells

A
Lymphoid Progenitor Cell
Early pro-B cell
Late pro-B Cell
Pre-B Cell
Dissociation as an Immature B
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7
Q

Lymphoid progenitor cell binds the stromal cell with…

A

CAMs

VLA-4 —– VCAM-1

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8
Q

Early pro-B binds to stromal cell with…

A

Kit —— SCF

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9
Q

Significant component of Late pro-B cell phase?

A

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

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10
Q

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

A

Bound by CAMs, still getting IL-7

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11
Q

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

A

Try the 2nd chromosome

If it still doesn’t work, apoptosis

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12
Q

Describe the pre-B cell receptor

A

mu heavy chain + surrogate light chain

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13
Q

What is a surrogate light chain?

A

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

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14
Q
As far as Ig gene rearrangements go, whats happening in...
Early Pro-B
Late Pro-B
Pre-B
Immature B
A

(H Chain) DJ Rearr
(H Chain) V-DJ Rearr
L Chain Rearr
Rearr ceases

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15
Q

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

A

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.

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16
Q

Successful arrangement will have what influence on the other chromosome

A

Shut it down

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17
Q

Value of allelic exclusion?

A

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

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18
Q

How does allelic exclusion happen?

A

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

19
Q

Why can’t the H chain rearrange?

A

Because of D genes btw V and J

Changing it would delete the other alleles

20
Q

What happens if L-chain arrangement is unproductive?

A

Vk1 can be replaced w/ Vk2
Works over and over till you run out of fragments
Do the same with Js

21
Q

What happens in negative selection?

A

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

22
Q

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

A

because the light chain can still rearrange

Rearrange until successful, or runs out of Js and apoptosis

23
Q

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

A

Signaled to undergo anergy

Switches to IgD and died shortly after

24
Q
Indicated by....
Recurrent Infections
No Visible Tonsils
Low-No Igs, No Mature Bs
Brother in same boat
Normal WBC Profile
A

X Linked agammaglobulinemia

25
Q

Cause of X-linked agamaglobulinemia?

A

Defect in Bruton’s tyrosine kinase

26
Q

Genetic inheritance of X-linked agammaglob.

A

Recessive, X-linked

27
Q

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

A

None.

28
Q

Describe the path of B cells through the LN

A

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

29
Q

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

A

They express adhesin molecules that let Bs in

30
Q

Chemokine that attracts B cell to HEV?

A

CCL21

31
Q

Chemokines that attract B cell into lymph node?

A

CCL21. CCL19

32
Q

Chemokine that attracts B cell into primary follice?

A

CXCL13

33
Q

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

A

Follicular Dendritic Cells

Cytokines

34
Q

What is BAFF?

A

B Cell Activating Factor

35
Q

Where does BAFF come from?

A

Goes from Folicular B Cells to BAFF receptor on B cell

36
Q

Role of BAFF in therapy

A

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

37
Q

What is lupus erthematosus?

A

Ab against connective tissue DNA

38
Q

What are B2 cells?

A

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

39
Q

How are B1 cells special?

A

Produced in fetus – live in peritoneal/pleural cavities
High Ig Production, Mostly IgM
Polyreactive

40
Q

Why know B cell tumor origin?

A

Origin may be reflected in tumor attributes

Esp. location

41
Q

Which B cell cancers are in BM and Blood

What origin?

A

ALL (Lymphoid Progenitor)

Pre-B cell leukemia (Pre-B)

42
Q

Which B cell cancer is almost only in BM?

What origin?

A

Multiple Myeloma (Like Plasma Cell)

43
Q

Where is Hodgkin’s Lymphoma?

A

Primarily in LN