BIOL 435 Ch. 9 (B-Cell Development)

Question 1

B-cell development begins in

Answer 1

• the bone marrow
• is completed in the periphery
• mature in the spleen

Question 2

immature B-cell

Answer 2

-exposed to self-antigens
>not until complete B-cell
*negative selection
-if good=leave bone marrow into blood to the spleen to mature

Question 3

stromal cells

Answer 3

• provides support and growth factors to developing cells
• interact with B-cells during development in bone marrow
• provide guidance to cause a B-cell, T-cell or other cells

Question 4

pre-B-cell receptor

Answer 4

• after VDJ rearrangement
• mainly intracellular, a few on membrane
• proliferation

Question 5

mature B-cells encounter antignes in

Answer 5

-secondary lymphoid organs

Question 6

bone marrow structure

Answer 6

• dynamic and complex
• stem cells
• stromal cells
• results in generation of a common lymphoid precursor (CLP)

Question 7

stem cells

Answer 7

-differentiate into many cell types

Question 8

stem cell factor (SCF)

Answer 8

-causes HSC to become a CLP

Question 9

CLP

Answer 9

-common lymphoid precursor
-be T or B cell
-if interacts with CXCL12
>pre pro B-cell to pro-B cell

Question 10

pro-B cell

Answer 10

-interact with IL-7 and become a pre-B cell

>pre-B cell will become an immature B-cell

Question 11

S1P

Answer 11

• sphingosine 1-phosphate
• signal from the blood
• interacts with immature B-cell, and tells it to leave the bone marrow and enter the blood

Question 12

bone marrow stromal cell-derived proteins

Answer 12

-indue early HSCs to beceom increasingly commited to the lymphoid lineage

Question 13

sequentially activated transcription regulators

Answer 13

• drive differentiation
  1. SCF
  2. CXCL12
  3. IL-7

Question 14

IL-7

Answer 14

• survival
• proliferation
• transcription of B-cell associated genes (recombination)
• B-cell commitment
• inhibits other signals

Question 15

later stages of B-cell development

Answer 15

• result in commitment to the B-cell phenotypes

* 2 checkpoints

Question 16

1st checkpoint

Answer 16

-between late pro-B and large pre-B
*when have expression of a functional pre-B-cell receptor
>H chain and SLC
-can try again if doesn’t work

Question 17

2nd checkpoint

Answer 17

• between small pre-B and immature B
• need a functional membrane bound IgM
• most get there and pass it

Question 18

immature B-cells in bone marrow

Answer 18

-exquistely sensitive to tolerance induction
>eliminate self-reactive cells
-surface receptors are tested against self-antigens

Question 19

3 outcomes when surface receptors are tested

Answer 19

1. Clonal deletion
2. Receptor editing
3. Anergy

Question 20

clonal deletion

Answer 20

• of strongly autoreactive cells by apoptosis

- occur within bone marrow: central tolerance

Question 21

receptor editing

Answer 21

• reactivation of light-chain recombination machinery
• may be primary mechanism
• occurs within bone marrow: central tolerance

Question 22

anergy

Answer 22

• induction of nonresponsiveness to further stimuli
• no proliferation or activation
• mechanism of self-tolerance outside the bone marrow

Question 23

deleted in bone marrow

Answer 23

-many, but NOT all self-reactive B-cells

Question 24

transitional cells

Answer 24

-functionally immature B-cells exported from the bone marrow

>enter perioarteriolar lymphoid sheath (PALS)

Question 25

transitional cells

Answer 25

-functionally immature B-cells exported from the bone marrow

Question 26

2 subsets of transitional cells

Answer 26

1. T1 2. T2 * important

Question 27

T1 and T2

Answer 27

-differ in gene expression as they progress through the spleen for further maturation into conventional, B2 cells

Question 28

T2 subset becomes

Answer 28

1. Follicular B-cells (migrate to lymph nodes and circulation) 2. Small % become marginal zone (MZ) B-cells >important for blood borne pathogens (remains in the spleen)

Question 29

categories of B-cells

Answer 29

1. B-1 B cells (not from HSC) 2. B-2 B cells >T1 >T2 (*3. MZ B-cell) >T3

Question 30

T1 subset

Answer 30

-is still undergoing screening >negative selection possible (BCR+Ag dependent) *surviving transition to T2 stage

Question 31

postive selection of T2

Answer 31

-survival signals (ex. BAFF) -T2 up regulates BAFFR and bind BAFF *competition=limited number of BAFF >many B-cells die

Question 32

BAFF

Answer 32

-B-cell activating factor belonging to the TNF family -tonic signal (all the time) -if binds to BAFFR on T2=survival signals >MATURE B-cell

Question 33

BAFF made by

Answer 33

- macrophages and dendritic cells | - more made during an infection to get more mature B-cells

Question 34

mature, primary B-2 B-cells

Answer 34

- migrate to lymphoid follicles - express high levels of IgM/IgD on their surface - recirculate between blood and lymphoid organs - help respond to Ag with T-cell help - 4.5months half-life in periphery

Question 35

help respond to Ag with T-cell help

Answer 35

-by producing Ab | >isotype switching after Ag activation

Question 36

T3 B-cells

Answer 36

- self reactive - may have been rendered anergic by contact with soluble self-Ag but not yet elminated - respond to Ag but don't divid, differentiate or secrete Ab->may die

Question 37

T3 B-cells maybe

Answer 37

-indicates another mechanism for peripheral tolerance | >induced after B-cells have matured and left the bone marrow/spleen microenvironments

Question 38

B-1 B-cells

Answer 38

-derived from a seperate developmental lineage (not HSC) >earlier in development -populate different anatomical niches than B-2 cells -constantly regenerated outside the bone marrow -30-50% of B-cells in pleural and peritoneal cavities of mice -relatively limited receptor repertoire -undergo apoptosis unless they interact with self Ag

Question 39

Tdt B-1 B-cells

Answer 39

-minimally expressed in the precursor of B-1alpha cells | >non-templated nucleotide diversity is more limited so little N region addition in Ab produced

Question 40

B1 B-cell receptors

Answer 40

-tend to bind microbial CHO Ags and lipids >bind with relatively low affinity >much more similar to PRRs of innate -act as a bridge between innate and adaptive

Question 41

B-1 B cells natural Ab

Answer 41

``` -secret them >most IgM >IgG or IgA -can secret them without binding an Ag >constantly secreting *are the first line of defense ```

Question 42

marginal zone cells

Answer 42

- found in white pulp outer regions of the spleen - specialized for blood-borne Ag recognition - low levels of IgD and Fc receptor - derived from T2 cells with strong self-Ag signalling through BCR

Question 43

blood-borne Ag recognition

Answer 43

-recognize protein and CHO Ags (similar to B-1 cells) | >some may be able to do so without T-cell help