Flashcards in B cell development Deck (29):
What regions make up the variable region of a heavy chain?
J region, V region, D region
What regions make up the variable region of a light chain?
J region, V region
How is diversity brought to Ab?
random combination of J, V, and D
random combination of light chain and heavy chain
Describe the process of recombination of light chain.
A V region and a J region are brought together via somatic recombination. Two regions are brought close together by a loop forming and being excised, followed by nucleotide insertions.
In what order do JVD come together on heavy chains?
D and J brought together first. V brought to the DJ complex. Nucleotide insertions connect the two segments as they are joining.
How are segments within the variable regions brought together?
RAG- recombinase genes bind certain sequences and pull the ends together to form the loop that gets excised
What is a signal joint? Where is in it?
the DNA between the V, D, or J segments that are being joined that is excised and eventually degrades, in the lariat
How are the V and J regions joined in light chains?
-involves 4 different codons to create "in frame" gene sequence coding for variable light chain
- RAG complex opens hairpins of DNA to generate palindromic P nucleotides
How are the V and DJ regions joined in heavy chains?
-RAG snips DNA, there are variable strands of NT bases left
-TdT adds random AAs (N nucleotides) on the free ends of DNA
-eventually overlap exists so repair enzymes can mend the strands together
When does terminal deoxynucleotidyl transferase exist?
during heavy chain arrangement only
What are two examples of non-functional rearrangments made by TdT?
-reading frame shift if the number of AA generated is not divisible by 3
-inserting stop codon
What is an early proB cell?
DJ heavy chain rearrangements on both chromosomes
What is a late proB cell? (checkpoint 1)
V-DJ rearrangement on 1st chromosome, if fails, V-DJ rearrangement on 2nd chromosome
-if it fails to put heavy chain on membrane in certain time to interact with surrogate light chain, it will apoptose
What is a preB cell?
Rearrange Kappa on 1st chromosome, if it fails, rearrange Kappa on 2nd chromosome, Lambda on 1st chromsome, Lambda on 2nd chromosome, then will apoptose
When is there a surrogate light chain? What does it signal?
It is in the pre Bcell stage to see if functional heavy chain has been produced. It signals light chain rearrangement if heavy chain rearrangement was successful or apoptosis if not.
How do you class switch from IgM to IgD?
Selective splicing of primary RNA transcript
Can you have IgM and IgD produced by the same cell?
Yes, signals in the environment can affect the splicing of RNA
Which constant region exon is for IgM and IgD?
mu for IgM, delta for IgD
How is secreted vs. membrane bound form of Ab determined?
alternative splicing of primary RNA transcript (same mechanism as IgM to IgD)
- 2 extra exons included for longer transmembrane form
Which form of Ab do active B cells produce: secreted or membrane bound?
How do you class switch from IgM to IgG? Is it permanent?
-DNA splicing form the same transcript due to signals from the environment
-variable region is joined to a new constant chain
-it is permanent
What chain is involved in class switch from IgM to IgG?
-constant regions brought together to form different heavy chains
-heavy chain switches
Is class switch regulated by RAG?
What enzyme mediates class switch and somatic hypermutation?
AID- activation-induced cytidine deaminase
What region and specific sites within it experience alteration during somatic mutation? Why?
-CDR1 and CDR2 (along with CDR3 are contact residues of Ag)
-yields improved binding to Ag they are selected for
When is the mutation frequency highest in the immune response?
-when B cells is most stimulated by T cells, as it undergoes class switch
-select B cells for with mutations in hypervariable region that binds better
What is different in T cell receptor formation from B cell? Why?
-educated in thymus not to recognize self and don't want to mutate to lose that self-recognition
What enzymes do both T cell and B cell receptor development processes use?
TdT and RAG