Ab diversity/B cell development (class) Flashcards
T/F each Ig molecule produced by any one B cell is identical
true
What is the complete collection of antibody (BCR) specificities generated by somatic recombination?
antibody repertoire
T/F each B cell displays many copies of the same BCR
on its surface
true
incredible repertoire of B cell receptors is generated via a unique genetic mechanism known as what?
somatic recombination
Describe the characteristics of somatic recombination
“totally” random process that is antigen-independent
mediated by two enzymes (RAG-1 and RAG-2; the
recombination activation genes)
In the lambda light chain locus, which parts are constant? describe how they are arranged…VJC
(L) V –V–V ——J–C—-J—C—–J—–C
C regions are constant, V and J are variable
In every B cell, which chain occurs first?
heavy chain always occurs first
Every B cell Ab is identical for what reason?
allelic exclusion
only 1 chromsosome is used at a particular time
pairing of V and J gene segments gives rise to many different what?
λ or κ light chain variable regions
pairing of V, D, and J gene segments gives rise to many different what?
heavy chain variable regions
Joining segments provide some diversity. But what gives the light more diversity to the coding region?
recombination of light chain when the joining of gene segments occurs because it is not precise
this gives it more generated
Why is Somatic Recombination of Ig Genes Such an Important Mechanism?
- the human genome contains approximately 40,000 genes
- the immunoglobulin genes code for up to 10^11 different antibody molecules (B cell receptors)
Give a general description of class switching
Change-Out of Constant Domains of the Heavy Chain
What is mutation that occurs at high frequency in the rearranged variable-region DNA of Ig genes in activated B cells, resulting in the production of variant antibodies, some of which have higher affinity for the antigen?
somatic hypermutation(affinity maturation)
Where does affinity maturation occur? and how it coincides with B cells?
- occurs in follicles in secondary lymphoid tissues
- B cells that express higher affinity Abs are positively selected
Cassette system of gene segments recombination occurs via what? describe it
somatic recombination
- antigen independent
- imprecise joining of gene segments
- pairing of rearranged light and heavy chains
What is ability of B cells to change the isotype of the Ab it produces (without changing the antigen specificity)? describe it
class switching
- antigen dependent
- this enables the immune system to select the type of Ab that is needed to best deal with the invading pathogen
Affinity maturation is synonymous with what?
somatic hypermutation
Is somatic hypermutation(affinity maturation) antigen dependent or independent?
antigen dependent
What enzyme is involved in signal transduction from cell-surface receptors during B cell development? What is this used for?
Bruton’s thymidine kinase (Btk)
B cell development
What genes make double- stranded breaks in DNA during somatic recombination? What is the reason for these?
recombination activation genes (RAG-1 and RAG-2)
B cell development
What enzyme catalyzes addition of N nucleotides at the junctions between rearranging gene segments? Why is this important
terminal deoxynucleotidyl transferase (TdT)
necessary for B cell development
What enzyme catalyzes switch recombination (class switching); also required for somatic hypermutation (affinity maturation)? Why is this important?
Activation-induced cytidine deaminase (AID)
B cell development
Describe the class switching WRT steps involved
- isotype switching signal received
- looping-out of DNA occurs
- switch region recombination occurs (intervening DNA is removed)