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IHO Week 2 > B Cell and T Cell Maturation > Flashcards

B Cell and T Cell Maturation Flashcards

1
Q

BCR complex includes

A

membrane-bound immunoglobulin (mIgM)

signaling chains CD79a and CD79b

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2
Q

earliest stage of antigen-independent B cell development

A

progenitor B cell stage (pro-B)

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3
Q

3 groups of pro-B cell

A

Early - express TdT alone
Intermediate - both TdT and CD45R
Late - CD45R, downregulated TdT

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4
Q

CD45R

A

receptor for growth and differentiation - remains expressed on surface throughout remainder of B-cell ontogeny

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5
Q

As B cells progress through pro-B cell stage -

A

rearrange Ig heave chain genes

begin to express CD43, CD19, RAG-1 and RAG2

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6
Q

As late pro-B pass into pre-B cell stage

A

downregulate TdT, RAG-1, RAG-2, and CD43 (regulates adhesion)

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7
Q

Pro-B cells also express c-Kit which

A

c-Kit which binds to stem-cell factor expressed on bone marrow stromal cells –> induces pro-B cells to proliferate and differentiate into pre-cursor B cells

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8
Q

CD43

A

pro-B cell - regulates adhesion

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9
Q

CD19

A

B cell co-receptor, works with CD21 and CD81

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10
Q

Pre-B cells can be divided into

A

large mitotically active pre-B and small non-dividing

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11
Q

both large and small pre-b express

A

Ig mu heavy chains in cytoplasm

pre-B cell receptor complex on surface

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12
Q

large pre-b cells have successfully

A

rearranged their Ig heavy chain genes

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13
Q

as pre-b pass from large to small

A

begin to rearrange Ig light chain genes and upregulate RAG1 and RAG2

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14
Q

Pre-b cells express

A

IL-7R and are stimulated to divide and differentiate using IL-7
secreted by bone marrow stromal cells

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15
Q

final stage B cell development

A

immature b-cell stage

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16
Q

immature b cells have successfully

A

rearranged their light chain gene and express IgM

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17
Q

expression immature B cells

A

RAG-1 and RAG-2 downregulated

Express IgM

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18
Q

As immature B cells develop into mature

A

begin to express both IgM and IgD
Then free to exit bone marrow and migrate to periphery
Go through transition stage

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19
Q

Cytokines required for B cell development

A

IL-7
Blys (B-lymphocyte stimulator) - important for survival of pre-immune B-cell stages
IL-4, IL-3 and low molecular weight B cell growth factor (L-BCGF) initiate B cell differentiation

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20
Q

transcription factors B cell development

A 
E2A, EBF
Pax5
Sox4 and LEF1
IRF4 and IRF8
Bcl-6

NOT Blimp-1 *supresses Bcl-6

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21
Q

E2A and EBF

A

coordinately activate early B-cell genes

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22
Q

Pax5

A

ensures development to B-cell lineages by restricting transcription of lineage inappropriate genes and activating expression of B-lineage signaling molecules

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23
Q

Sox4 and LEF1

A

promote survival and proliferation of pro-B cells

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24
Q

IRF4 and IRF8

A

terminate pre-BCR signaling by IRF4 and promote differentiation to small pre-B cells

25
Q

Bcl-6

A

required for germinal B-cell differentiation and generation of memory B-cells

26
Q

Blimp-1

A

suppresses Bcl-6 expression and is required for development of Ig secreting cells and maintenance of long lived plasma cells.

27
Q

XLA

A

a block at the pro-B cell to large pre-B cell transition in the bone marrow.
This defect is mostly caused by a mutation in the gene encoding the enzyme Bruton’s tyrosine kinase (Btk). Btk is a key enzyme involved in signal transduction downstream of the pre-BCR and BCR.
XLA patients have very few circulating B-cells and negligible serum immunoglobulin (Ig).

28
Q

Common variable immunodeficiency (CVID)

A 
CVID manifests in reduced serum Ig, memory B-cells, class switch recombination and B-cell activation. 
Mutations in CD40 ligand on T-cells, B-cell surface receptor CD19, activated T-cell costimulatory molecule ICOS, and TACI (another receptor for Blys) have all been identified in CVID patients.
29
Q

Negative selection of Self-reactive B cells

A

occurs in bone marrow (clonal deletion)
limits ab-mediated autoimmunity
also some occurs in periphery because not all self-antigen is expressed in bone marrow

30
Q

If immature b cells express mIgM recognizing self-antigen

A

Some of the immature B cells undergo apoptosis
Some of the immature B cells undergo editing of light chain genes to produce a different light chain that (when combined with the heavy chain) does not recognize self-antigen.

31
Q

3 major populations of B cell in periphery

A

Follicular (B2) B cells
B-1
Marginal zone

32
Q

which B cells require T cell help

A

B-2, sometime marginal zone

33
Q

which B cells do not require T cell help

A

B-1

34
Q

B-1 release what isotypes

A

IgM

35
Q

B-2 release what isotypes

A

IgG

36
Q

What kind of antigens do B-1 respond to

A

carbohydrates (some protein)

37
Q

What kind of antigens do B-2 respond to

A

proteins (some carbs)

38
Q

Which kinds of B cells have memory

A

Mostly B-2 (TD), B-1 (T-I) has very little

39
Q

B-1 found mainly where

A

peritoneum and pleural cavitites

40
Q

B-2 found mainly where

A

secondary lymphoid organs

41
Q

marginal zone B cells found where

A

marginal zones of the spleen

42
Q

B-1 cells ID by expression of

A

CD5 - induced upon binding of TI antigens

43
Q

which b cells can self renew

A

B-1
not B-2 *from precursons in bone marrow
marginal maybe

44
Q

Intracellular signaling in B cell activation

A

BCR receptor plus something required. (2BCRs, BCR + coreceptor). IgM or IgD bind. If cross-linked, then CD79a/b activate signaling through their ITAM repeats (immunoreceptor tyrosine-based activation motif). Cascade of signaling leads to the eventual activation of the transcription factor NF-kB and G proteins that activate the transcription factors Rho, Rac, and Ras.

45
Q

two groups of TI-antigens

A

TI-1 antigens are predominantly bacterial cell wall components – the prototypical TI-1 antigen is lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria

TI-2 antigens are predominantly large polysaccharide molecules with repeating antigenic determinants (e.g. Ficoll, dextran, polymeric bacterial flagellin, and poliomyelitis virus)

46
Q

TI-antigens activate

A

B-1 cells

47
Q

Many TI-antigens are

A

PAMPs that can be recognized by TLRs

48
Q

B cell response to TI-1 antigen

A

B1 B cells bind to LPS either through TLR4 or the BCR.

TLR4 = nonspecific (polyclonal activation).
BCR = specific (clonal activation).

Type 1 TI antigens can stimulate both immature and mature B cells through the use of TLR4.
Only IgM is produced in response to this stimulation.

49
Q

B cell response to TI-2 antigen

A

B1 B cells bind to Type 2 TI antigens through the cross-linking of the BCR.

BCR = specific (clonal activation).
Type 2 TI antigens can only stimulate mature B cells through the use of the BCR.
Mostly IgM is produced in response to this stimulation.
CD4+ Th2 T cells can be involved to produce cytokine for a full B cell response that can include class-switching.

50
Q

IL-4 induces what CSR

A

IgG, IgE

IgG1

51
Q

TGF-b induces what CSR

A

IgA, IgG

IgG2b

52
Q

IL-5 induces what CSR

A

IgA

53
Q

IFNg induces what CSR

A

IgG3, IgG2a

54
Q

At what stage of T cell development is TCR undergoing somatic mutation/recombination?

A

Double negative (DN 1-4)

55
Q

Changes in TCR during development

A

pre-TCR = TCRb, working on TCRa
Mature-TCR but not signaling = +/- selection
Mature abTCR and signaling = proliferation, differentiation, survival

56
Q

Stages of B cell maturation

A 
Stem cell
Pre-pro
Pro B cell (early and late)
Pre B cell (large --> small)
Immature B cell
Mature B cell 
Activated B cell --> memory, plasma
57
Q

XLA usually what defect

A

Btk - transduction downstream of pre-BCR and BCR (cannot receive stimulation to grow)

58
Q

What transcription factors in Germinal Center (SHM and CSR)

A

Pax 5, Bcl-6

59
Q

What transcription factors in Plasma Cell (–> abs)

A

IRF-4, BLIMP-1

IHO Week 2 (13 decks)

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