B cells: generation of bcr and tcr diversity II

Question 1

Tcr structure

Answer 1

Composed of alpha nd beta chain
Each has variable and constant region

Question 2

Describe tcr - alpha chain locus

Answer 2

Has multiple v and j segments

Question 3

Describe tcr - beta chain locus

Answer 3

Has multiple v and d and j segemnets

Question 4

Describe tcr rearrangement = somatic recombination

Answer 4

Takes place in thymus
Irreversible

Question 5

DESCRIBE COMBINATORIAL DIVERSITY OF TCR

Answer 5

Vj in alpha chain
Vdj in beta chain - dj first then v dj
Then combine alpha and beta chains

Question 6

DESCRIBE mechanism of v(d)j recomb of tcr= similarities to bcr

Answer 6

V d j segments flanked by rss
Rag1/2 recognizes sequences rss
Artemis cuts dna hairpins
Tdt adds non coded nts in joining regions

Question 7

DESCRIBE mechanism of v(d)j recomb of tcr= differences to bcr

Answer 7

Ig heavy chain —> d segment surrounded by 2 rss, both 12 bp spacing
Tcr beta chain —> d segments have a r’ 12bp rss an a 3’ 23bp rss (rule still applies)

Question 8

Does tcr have cdrs

Answer 8

Yesss
3 cdrs per chain

Question 9

Describe cdrs on tcrs

Answer 9

Sites with most diversity

Question 10

Describe cdr1 and 2 for tcrs

Answer 10

Encoded within v segments fo alph and beta chains

Question 11

Describe cdr3 for tcrs

Answer 11

Cdr3 = particularly important source of diversification - hyper variable
Encoded in d and j segments of beta chain between the v and j segments fo alpha chain

Question 12

What is allelic exclusion

Answer 12

Ensures that each B cell synthesizes only one allele for a heavy and one allele for a light chain

Question 13

What happens once B cell receptor expressed on surface of developing cell

Answer 13

= sends signal to silence part of gene that codes for other chromosome

Question 14

What happens to other chromosomes during alleic exclusion

Answer 14

Becomes methylated and inaccessible to transcription machinery
Genomic silencing of other chrom = ensures each B cell willl only express the same copy of bcrs that have same specificity

Question 15

First wave secreted abs

Answer 15

Igm and igd

Question 16

Describe what mature naive bc cells express

Answer 16

Tm igm and igd
Initially = newly formed B cells express igm as primary B cell receptors
Later = some of these B cells switch to expressing igd
= igm and igd co expressed on B cell surface

Question 17

Describe after mature naive B cells get signals 1 and 2

Answer 17

—> some form primary focus and become plasma blasts capable of secreting ab

Question 18

How does the B cell start secreting abs and how does it change production of ig subtypes

Answer 18

Alternative rna splicing
Removes one of those constant regions of abs = changes type of ab

Question 19

What do B cells produce - alt splicing

Answer 19

Long primary mRNA transcript that is differnitally spliced to yield either 2 of distinct mRNA molecules

Question 20

What are the result of alternative splicing

Answer 20

Secreted and trans membrane mRNA = result of rna splicing too
(Splice out part responsible fro secreting to anchoring bcr, choose one)

Question 21

Describe ig classes = summarize

Answer 21

5 isotopes of heavy chain
Depending on isotope = 5 diff classes igs igm,igd, igg, iga, ige
Variants of igg and iga classes

Question 22

How do we switch from producing standard igm and igd to other subtypes

Answer 22

= secondary diversification
B cells undergo processes to produce more effective abs in germinal centre =
Somatic hypermutation
Affinity maturation
Class switching

Question 23

Where does secondary diversification happen

Answer 23

In germinal cengter - after B cell has received signals 1 and 2 again

Question 24

What is somatic hyper mutation

Answer 24

Leads to higher affinity - better lock and key for its ag
Specificity remains the same tho

Question 25

What is class switching

Answer 25

Process that replaces one heavy chain constant region with one of diff isotope

Question 26

Where do somatic hypermutation and class switching act on

Answer 26

Mechanisms act on already rearranged igd genes V(d)j recomb has occurred in variable region —> cannot go back

Question 27

What does somatic hypermutation operate on

Answer 27

Operates on activated B cells in peripheral lymphoid organs In germinal centre of lymh nodes High rate of point mutations in v gene sequences that improve ag binding

Question 28

Describe affinity maturation

Answer 28

Selects for survival of mutated B cells that have a high affinity for ag

Question 29

What also occurs during secondary or tertiary responses

Answer 29

Somatic hypermutation = get higher affinity abs, = why secondary responsive more robust and effective

Question 30

Describe class switching = what informs class switching

Answer 30

Cytokines secreted by tfh in germinal centre will inform class switching = ifnelucne B cell = tell which abs to produce Ex = type 2 response cytokine il4 induces ige

Question 31

When does class swicitng happen

Answer 31

Only occurs after B cell activation

Question 32

Is clas switching reversible

Answer 32

Naha Irreversible

Question 33

Describe class switching image/process

Answer 33

Class switch recombination guided by switch regions located upstream of each c gene Aid = created nicks in switch regions, everything in middle = excised Next c gene seen = determined isotope, so becomes a certain class of ab

Question 34

Does somatic hypermutation always make affinity better

Answer 34

No its random = can also reduce ag binding affinity Maturation = survival of fittest = only ensues that B cells that have higher binding to ag survive