B-cell Development and Antibody Production - Borghesi Flashcards
Where are fetal B-cells derived and how are they different from adult B-cells.
Fetal B-cells are derived from hematopoetic stem cells in the fetal liver and mature into B1 cells. They have a limited repertoire (all IgM).
Where are adult B-cells derived and how are they different from fetal B-cells.
Adult B-cells are derived from the bone marrow and mature into B2 cells. They have a massively diverse repertoire and are the source of memory unlike fetal B-cells.
What are some of the hallmarks of adaptive immunity?
- Clonality - Each B-cell produces Ig’s of a unique specificity.
- Specificity - Each receptor binds to a unique antigen.
- Diversity - Millions of different antigen specificities exist at any given time.
What are the functions of antibodies?
- Prevents dissemination of pathogen
- Inhibit pathogen replication
- Activate complement
- Bind to Fc receptors on macrophages, DCs, NK cells
Are antigen-antibody interactions covalent or not? Why is this important?
Antigen-antibody interactions are non-covalent. This is important because the longer the antigen sits in the binding pocket, the more persistent the signaling.
What are some shared structural features between Igs and TCRs?
Igs have a light and heavy chain composing the antigen binding sites, similar to how TCRs have alpha and beta chains composing their antigen binding sites.
What is a key difference between antibodies (Igs) and TCRs?
Antibodies can be both membrane-bound and secreted whereas TCRs are only membrane-bound.
VDJ Recombination: Step 1
Recombinational Signal Sequence (RSS) in V and J genes are recognized by Rag1/2.
VDJ Recombination: Step 2
Rag complex cuts a single strand of DNA, exposing a free 3’ hydroxyl.
VDJ Recombination: Step 3
Free 3’ OH introduced by Rag complex attacks the other strand resulting in a complete double stranded break and hairpin formation.
VDJ Recombination: Step 4
Artemis enzyme removes the hairpinned DNA.
VDJ Recombination: Step 5
TdT (terminal deoxynucleotidyl transferase) adds or deletes non-coded nucleotides, permanently changing the DNA sequence.
VDJ Recombination: Step 6
DNA repair enzymes join V segments with J segments. DNA that used to be between these segments form a signal joint and are lost.
Example Question: What would happen in an infant with a null mutation in the Rag gene?
No B or T-cell development.
Example Question: What would happen in an infant with partial loss of function in Rag?
Autoimmunity due to lack of regulatory B and T cells, therefore no immune dampening.