Generation of antibody diversity Flashcards
What could classical models not account for when it comes to diversity in Ig?
- The diversity of antigen-binding specificities, 2. Ig-heavy and Ig-light chains with variable N-terminus and constant C, 3. Diff antibody classes with same antigenic specificity
What’s the Dreyer and Bennett model?
V-genes and C-genes encoded by separate genes which create one protein
Where are the lambda, kappa and heavy chain genes found on the human chromosome
22, 12, 14
What are the light chains encoded by?
V and J gene segments
What are the heavy chains encoded by?
V, D and J gene segments
What is combinatorial diversity?
Recombination of gene segments creating different V region exons
What is RSS
Recombination signal sequences - conserved heptamers and nonamers that flank gene segments
What is the spacing between RSS’
23 or 12 nucleotides
What is recombination catalysed by?
V(D)J recombinase which is lymphoid specific recombination - activates genes RAG-1 and RAG-2
What two joints are produced?
Coding joint and signal joint
What is junctional diversity?
Addition and subtraction of nucleotides at joints between gene segments
What does TdT do?
N-nucleotide addition
How is diversity increased?
Somatic hypermutation
What does somatic hypermutation do?
Targets rearranged gene segments encoding the variable region
What regions are does somatic hypermutation particularly occur at?
CDR
What are initially co-expressed on B cell surface?
IgM and IgD
What are the two forms of IgM and how do they occur?
Alternative splicing: membrane bound or secreted
mRNA with M segments & poly A signal
Membrane bound
mRNA with S segments & poly A signal
Secreted
What is class switching?
After antigenic stimulation, V gene combines with any C gene to create new antibody class with same antigen binding site
What dictates which antibody class is made
Cytokines
What does class switching involve?
Recombination of heavy chain constant region genes
What is AID?
Mutation in the VDJ region
What does B cell development depend on?
Antigens
