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MIMM 214 > B Cells 5 > Flashcards

B Cells 5 Flashcards

1
Q

what are the 4 proteins involved in BCR diversity and their roles?

A
  1. RAG1/2 –> brings specific segments of DNA together
  2. Artemis –> cuts DNA at hairpin
  3. Exonuclease –> removes some nt for joining
  4. TdT –> excess trimming at D junction of heavy chain
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2
Q

what are the 2 chains of TCR and their regions?

A

ALPHA –> multiple V and J, 1 C
BETA –> multiple V, D, J, 1 C

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3
Q

what is the recombination of TCR called?

A

somatic recombination

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4
Q

where does somatic recombination occur? reversible or irreversible?

A

occurs in thymus

IRREVERSIBLE

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5
Q

what are the 4 similarities with TCR and BCR recombination?

A
  1. V, D, and J are flanked by RSS
  2. RAG1/2 recognizes these sequences
  3. artemis cuts DNA hairpins
  4. TdT adds non-coded nucleotides in joining regions
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6
Q

what is the difference btwn TCR and BCR recombination?

A

in Ig heavy chain, the D segment is surrounded by 2 RSS, both with 12 bp –> 12(D)12

In TCR beta chain, the D segment is surrounded by 12 and 23 RSS –> 12(D)23

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7
Q

do TCRs have CDRs?

A

yes

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8
Q

describe the diversity of TCR

A

CDRs are the sites in TCR with the most diversity

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9
Q

which CDR is the most important for diversity of TCR?

A

CDR3

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10
Q

where are CDR1 and CDR2 encoded?

A

CDR1 and CDR2 encoded within the V segment of alpha and beta chains

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11
Q

where is CDR3 encoded?

A

CDR3 encoded within the D and J segments of TCR chain

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12
Q

what is allelic exclusion?

A

ensures that each B cell synthesizes only 1 allele for the heavy chain and 1 allele for the light chain

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13
Q

how does allelic exclusion work?

A

both alleles from each parent is PRESENT but only 1 is expressed and silences the gene for the other allele

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14
Q

how does the non-expressed allele become silenced by the expressed allele?

A

the expressed allele sends a signal to silence the part of the gene that codes for the other chromosome

the chromosome becomes methylated and inaccessible to transcription machinery

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15
Q

why does allelic exclusion occur?

A

to ensure B cells only express copies of BCRs with the same specificity

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16
Q

which 2 types of Ig are part of the FIRST WAVE of secreted antibodies?

A

IgM and IgD

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17
Q

what do mature naive B cells express initially?

A

initially, newly formed B cells express IgM as their primary B cell receptors

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18
Q

what do mature naive B cells express after IgM?

A

after expressing IgM, B cells will switch to expressing IgD

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19
Q

how are IgM and IgD expressed on B cell surface?

A

IgM and IgD co-expressed on B cell surface

20
Q

what happens to mature naive B cells once they are activated on by signal 1 and 2?

A

upon activation by signal 1 and 2, some can form primary focus and become plasmablasts that secrete IgM or IgD

21
Q

what allows the B cell to start secreting antibodies and how does it change the production of Ig subtypes?

A

ALTERNATIVE RNA SPLICING

22
Q

what does alternative RNA splicing do to make specific Ig subtypes?

A

all DNA in B cells is transcribed into long primary mRNA transcripts which are spliced into 2 types of mRNA molecules i.e. splice out exons for the Ig you don’t want

23
Q

what happens during alternative RNA splicing when we want IgD?

A

if we want IgD, the IgM RNA exons will be spliced out (vice versa if we want IgM)

24
Q

what does alternative RNA splicing do to allow antibody secretion?

A

certain carboxy terminus for transmembrane Ig vs secreted Ig so you splice out the terminus you don’t want

25
Q

what are the 5 isotypes of heavy chains?

A

M (mu)
D (delta)
G (gamma)
A (alpha)
E (epsilon)

26
Q

how do we switch from producing different subtypes of Ig?

A

different heavy chain gives different Ig class

27
Q

which Ig classes have varianets?

A

IgG and IgA

28
Q

how many possible constant regions are there for all Ig?

A

9

29
Q

are the types of constant regions the same or different for diff species?

A

the constant regions are different in different species

30
Q

what is another name for secondary lymphoid follicle?

A

germinal centre

31
Q

what happens in the secondary lymphoid follicle/germinal centre?

A

activated B cells become plasma cells and secrete antibodies with DIFFERENT ISOTYPES and HIGHER AFFINITY than antibodies initially produced by plasmablasts

32
Q

what are the 3 processes for B cells to make antibodies that are more effective when they are plasma cells?

A
  1. somatic hypermutation
  2. affinity maturation
  3. class switching
33
Q

what occurs during secondary diversification?

A
  1. somatic hypermutation
  2. affinity maturation
  3. class switching
34
Q

where does secondary diversification occur?

A

in germinal center

35
Q

when does secondary diversification occur?

A

once B cell has received signal 1 and 2

36
Q

what occurs during somatic hypermutation?

A

gains a higher affinity for its antigen but its specificity remains the same

37
Q

what occurs during class switching?

A

replaces 1 heavy chain constant region with one of a different isotype

38
Q

what do somatic hypermutation and class switching act on?

A

act on Ig genes that have already been rearranged –> VDJ recombination has already occurred

39
Q

what does somatic hypermutation act on and where do it occur?

A

acts on activated B cells in germinal centers peripheral lymphoid organs (where B cells activate)

40
Q

how does somatic hypermutation occur? (2)

A
  1. high rate of random point mutations in V gene sequences that improve or decrease Ag binding
  2. mutations that increase affinity for Ag are selected
41
Q

what is affinity maturation?

A

the selection of mutations with increased Ag affinity in somatic hypermutation

42
Q

why does somatic hypermutation occur during secondary and tertiary responses?

A

to get antibodies with increasingly higher affinity so you get a better response each time

43
Q

what causes class switching?

A

cytokines secreted by follicular helper T cells in germinal center

44
Q

when does class switching occur?

A

after B cell activation

45
Q

is class switching reversible or irreversible?

A

irreversible

46
Q

what guides class switch recombination?

A

class switch recombination is guided by SWITCH REGIONS that are upstream of each constant gene

47
Q

describe the process of class switching (3)

A
  1. enzyme makes double strand break in switch region
  2. this cuts out a portion of DNA with some constant regions, leaving some constant regions remaining
  3. the constant region that is upstream of VDJ will be expressed

MIMM 214 (33 decks)

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