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Spring 2022 > BIOL 435 Ch. 9 (B-Cell Development) > Flashcards

BIOL 435 Ch. 9 (B-Cell Development) Flashcards

1
Q

B-cell development begins in

A
  • the bone marrow
  • is completed in the periphery
  • mature in the spleen
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2
Q

immature B-cell

A

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

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3
Q

stromal cells

A
  • 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
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4
Q

pre-B-cell receptor

A
  • after VDJ rearrangement
  • mainly intracellular, a few on membrane
  • proliferation
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5
Q

mature B-cells encounter antignes in

A

-secondary lymphoid organs

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6
Q

bone marrow structure

A
  • dynamic and complex
  • stem cells
  • stromal cells
  • results in generation of a common lymphoid precursor (CLP)
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7
Q

stem cells

A

-differentiate into many cell types

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8
Q

stem cell factor (SCF)

A

-causes HSC to become a CLP

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9
Q

CLP

A

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

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10
Q

pro-B cell

A

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

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

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11
Q

S1P

A
  • sphingosine 1-phosphate
  • signal from the blood
  • interacts with immature B-cell, and tells it to leave the bone marrow and enter the blood
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12
Q

bone marrow stromal cell-derived proteins

A

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

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13
Q

sequentially activated transcription regulators

A
  • drive differentiation
    1. SCF
    2. CXCL12
    3. IL-7
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14
Q

IL-7

A
  • survival
  • proliferation
  • transcription of B-cell associated genes (recombination)
  • B-cell commitment
  • inhibits other signals
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15
Q

later stages of B-cell development

A
  • result in commitment to the B-cell phenotypes

* 2 checkpoints

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16
Q

1st checkpoint

A

-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

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17
Q

2nd checkpoint

A
  • between small pre-B and immature B
  • need a functional membrane bound IgM
  • most get there and pass it
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18
Q

immature B-cells in bone marrow

A

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

19
Q

3 outcomes when surface receptors are tested

A
  1. Clonal deletion
  2. Receptor editing
  3. Anergy
20
Q

clonal deletion

A
  • of strongly autoreactive cells by apoptosis

- occur within bone marrow: central tolerance

21
Q

receptor editing

A
  • reactivation of light-chain recombination machinery
  • may be primary mechanism
  • occurs within bone marrow: central tolerance
22
Q

anergy

A
  • induction of nonresponsiveness to further stimuli
  • no proliferation or activation
  • mechanism of self-tolerance outside the bone marrow
23
Q

deleted in bone marrow

A

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

24
Q

transitional cells

A

-functionally immature B-cells exported from the bone marrow

>enter perioarteriolar lymphoid sheath (PALS)

25
Q

transitional cells

A

-functionally immature B-cells exported from the bone marrow

26
Q

2 subsets of transitional cells

A
  1. T1
  2. T2
    * important
27
Q

T1 and T2

A

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

28
Q

T2 subset becomes

A
  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)
29
Q

categories of B-cells

A
  1. B-1 B cells (not from HSC)
  2. B-2 B cells
    >T1
    >T2 (*3. MZ B-cell)
    >T3
30
Q

T1 subset

A

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

31
Q

postive selection of T2

A

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

32
Q

BAFF

A

-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

33
Q

BAFF made by

A
  • macrophages and dendritic cells

- more made during an infection to get more mature B-cells

34
Q

mature, primary B-2 B-cells

A
  • 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
35
Q

help respond to Ag with T-cell help

A

-by producing Ab

>isotype switching after Ag activation

36
Q

T3 B-cells

A
  • 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
37
Q

T3 B-cells maybe

A

-indicates another mechanism for peripheral tolerance

>induced after B-cells have matured and left the bone marrow/spleen microenvironments

38
Q

B-1 B-cells

A

-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

39
Q

Tdt B-1 B-cells

A

-minimally expressed in the precursor of B-1alpha cells

>non-templated nucleotide diversity is more limited so little N region addition in Ab produced

40
Q

B1 B-cell receptors

A

-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

41
Q

B-1 B cells natural Ab

A 
-secret them
>most IgM
>IgG or IgA
-can secret them without binding an Ag
>constantly secreting
*are the first line of defense
42
Q

marginal zone cells

A
  • 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
43
Q

blood-borne Ag recognition

A

-recognize protein and CHO Ags (similar to B-1 cells)

>some may be able to do so without T-cell help

Spring 2022 (54 decks)

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