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micr 386 > module 03 section 03 (B-cell development) > Flashcards

module 03 section 03 (B-cell development) Flashcards

1
Q

B cell development has antigen- ____ and ____ phases

A

independent or dependent

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2
Q

describe (generally) what happens in the antigen-independent phase

A

a single progenitor cell gives rise to a large number of lymphocytes

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3
Q

what is eliminated during the antigen-independent phase?

A

cells identified as self-reactive are selectively eliminated

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4
Q

what is the result of the antigen-independent phase?

A

the generation of immunocompetent, mature B-cells in the bone marrow that can bind to a unique antigen

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5
Q

define “immunocompetent”

A

denoting a mature lymphocyte that is capable of recognizing a specific antigen and mediating an immune response

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6
Q

what are the two factors that result the ability of a mature B-cell to bind to a unique/specific antigen?

A

(1) V-(D)-J rearrangement

(2) allelic exclusion

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7
Q

define “V-(D)-J rearrangement”

A

process that ensures clonally unique Ig variable regions (which specifically bind an antigen), ultimately creating Ig diversity

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8
Q

define “allelic exclusion”

A

ensures that each B-cell expresses a single antibody on the surface, ensuring specificity

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9
Q

what does the antigen-dependent phase require for initiation? (2)

A

(1) B-cell activation by antigen binding and (2) co-stimulatory singals from helper T-cells

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10
Q

stimulatory signals from helper T-cells promote:

A

B-cell differentiation into either memory B-cells or antibody secreting plasma cells

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11
Q

describe (generally) what heppens during the antigen-dependent phase

A

this phase involves B-cell proliferation, antibody affinity maturation, and antibody class switching

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12
Q

where do the processes of the antigen-dependent stage occur?

A

all in the germinal centers of secondary lymphoid tissues

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13
Q

what is required by the processes of the antigen-dependent phase?

A

several surface associated proteins and transcription factors

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14
Q

define “affinity maturation”

A

the increase in average antibody affinity for an antigen that occurs during the course of an immune response OR in subsuquent exposures to an antigen

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15
Q

what happens to B-cells if there is no antigen activation?

how prevalent is this?

A

cell death (90% of cases)

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16
Q

the early stages of B-cell development are dependent on which type of cells?

A

bone marrow stromal cells

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17
Q

what are stromal cells?

A

CT cells of an organ

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18
Q

list the steps of the early development processes by which pro B-cells become immature B-cells (5)

what is the end result?

A

(1) lymphoid progenitor cells bind VCAM-1 (on bone marrow stromal cell) via integrin VLA-4 which acts as anchors
(2) VCAM-1 binding promotes the binding of early pro B-cell surface c-Kit receptor (tyr kinase) to SCF on the stromal cell surface
(3) the kinase is activated, VDJ rearrangement of IgM heavy chain occurs
(4) IL-7 is required to drive proliferation and survival of pre B-cell from late pro to pre B-cell
(5) pre B-cells lose their independence on SCF and cease to express c-Kit causing the cell to detach from the bone marrow stromal cell
- end result = immature B-cell

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19
Q

once the pre B-cell becomes an immature B-cell via light chain rearrangement, it may undergo:

A

further mechanisms, such as receptor editing

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20
Q

what is the first gene rearrangement that occurs during B-cell development? what is the result?

A
  • D-J rearrangement of the heavy IgM

- changes a pro B-cell to an early pro B-cell

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21
Q

mutations to the RAG enzymes or mutions in the heavy J segment leads to:

A

lack of development of early pro B-cells

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22
Q

what is the second gene rearrangement that occurs during B-cell development? what is the result?

A
  • V-D-J rearrangement
  • successful v-d-j rearrangement gives rise to the heavy chain of IgM (expressed on cells surface)
  • changes early pro B-cell to pre B-cell
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23
Q

unsuccessful V-D-J rearrangement leads to what?

A

cell death

24
Q

in order for heavy chain IgM to be expressed on the cell surface, It has to:

A

be in association with the surrogate light chain

25
Q

what prevents the expression of heavy chain IgM on the cells surface?

A

the gene knockout for the transcription factors lambda 5 or pax 5 or the gene for heavy chain IgM

26
Q

what type of cell is the IgM heavy chain expressed on?

A

the pre B-cell expresses the heavy IgM chain associated with the surrogate light chain

27
Q

the surrogate light chain expressed on the cell’s surface triggers:

A

rearrangement of the light chain (as kappa or lambda)

-i.e. third rearrangement

28
Q

what is the third gene rearrangement that occurs during B-cell development? what is the result?

A
  • V-J rearrangement of the light chain
  • light chain associates with the heavy chain IgM on the cells surface
  • changes pre B-cell to immature B-cell
29
Q

within the bone marrow, newly developped immature B-cells (with IgM) that recognize self antigens:

A

may go through a clonal deletion process which leads to the death of self reactive B-cells

30
Q

can self reactive B-cells be rescued from clonal deletion?

why or why not?

A

yes - by undergoing further receptor editing of the light chain, so that the heavy chain can associate with a different light chain
-results in an anitbody with different specificity for an antigen

31
Q

both clonal deletion and receptor editing are types of what?

A

negative selection

32
Q

does positive selection occur before or after negative selection?

A

after

33
Q

what is the result of positive selection?

A
  • the expression of IgD on the cells surface together with IgM
  • which gives rise to the mature B-cell
34
Q

partial immunoglobulin molecules combine with ___(1)___ in the developing B-cell to direct ___(2)___

A

(1) invariant chains

(2) gene rearrangement

35
Q

can Mu heavy chains be expressed on the cell surface on their own?

A

no

36
Q

because IgM heavy chain can not be expressed on its own, pre B-cells produce:

A

a surogate light chain which is composed of 5lambda and VpreB (similar to VL but with extra aa sequences)

37
Q

explain how Mu chains are expressed on cell surfaces

A

in an immunoglobulin like complex with a surrogate light chain and signal-tranducting Iga and IgB heterodimers

38
Q

what does signalling via the Mu:lambda5:VpreB Ig-like molecule trigger?

A

(1) pre B-cell proliferation and survival
(2) stops further heavy-chain gene rearrangement
(3) induces light chain gene rearrangement

39
Q

what would happen if there were defects in the surrogate light chain

A

no B-cells would be produced

40
Q

what is another term for negative selection?

A

central tolerance

41
Q

define “negative selection”

A

the process of eliminating developing B-cells that recognize self-antigen

42
Q

what does negative selection ensure?

A

that the immune system does not attack self peptides

43
Q

what are the two mechanisms by which negative selection takes place?

A

clonal deletion and receptor editing

44
Q

explain clonal deletion

A

apoptosis of immature B-cells that have expressed receptors that recognize self-antigen before developing into fully immunocomptent mature lymphocytes

45
Q

what does clonal deletion prevent?

A

recognition and destruction of self host cells

46
Q

explain receptor editing

A
  • immature self reactive B-cells with active RAG can be rescued from clonal deletion by editing their light chains (rearrangement)
  • rare
47
Q

rearranged light chains can alter:

A

the specificity of the antibody by replacing that which offers autoreactivity with one that does not

48
Q

immature B-cells that have already undergone VDJh rearrangement still express surrogate light chains, true or false? why or why not?

A

false - instead they express kappa or lambda light chains together with the Mu heavy chains to form IgM

49
Q

in addition to lambda/kappa light chains and the Mu heavy chain, immautre B-cells will also express:

A

the Iga-IgB heterdimer

50
Q

when do immature B-cells become mature B-cells?

A

when the light chain rearrangement has stopped

51
Q

every B-cell has the potential to produce 2 different antibodies, what are they?

A

one from rearrangement of the maternal loci and one from the paternal loci

52
Q

do antigens have one or two specificities?

A

one

53
Q

explain allelic exclusion

A
  • the completion of a successful rearrangement of the first allele results in inactivation of the second allele
  • basic concept: one B-cell has on antigenic specificity
54
Q

what does allelic exclusion ensure?

A

that functional B-cells never contain more than one VDJ(H) and VJ(L) unit

55
Q

allelic exclusion suggests that once a productive VDJ(H) rearrangement and a productive VJ(L) rearrangement have occured:

A

the recombination machinery is turned off so the heavy and light chain genes on the homologous chromosomes are not expressed

56
Q

the transition from an immature B-cell to a mature B-cell is associated with:

A

(1) expression of both IgM and IgD on the cell surface
(2) both Ig heavy chains on each cell having the same V region
(3) both Ig heavy chains are associated with the same light chains

57
Q

do IgM and IgD on a mature B-cell have the same specificity ?

A

yes

micr 386 (31 decks)

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