Adaptive immunity, cells & functions – B-cells Flashcards
What is an expanded B-cell clone (clonal selection)?
One or multiple B-cells that were presented the same antigen and proliferated (selected to expand due to its BCR-specificity)
What is the receptor of a B-cell?
Antibody (Ab) = Immunoglobulin (Ig) = B cell receptor (BCR)
There is the membrane-bound and secreted forms
What is the total numbers of distinct naïve B-cell clones?
~5x10^13 =
50’000’000’000’000
Where does the VDJ recombination happen, from what enzyme and in what order?
- this happens in the bone marrow where the B-cells are formed
- RAG1/2 enzyme allows the recombination
- first D-J combination than V-DJ combination
What is the positive & negative selection in B-cell maturation in the bone marrow and what’s the point of it?
Positive selection: check if B-cell receptor is functional (50-75% are than self-reactive) Negative selection (central tolerance): clear the self-reactive B-cells (20-40% are than still self-reactive) Negative selection (peripheral tolerance): second turn of clearing self-reactive B-cells, B cells can become anergic in the absence of the correct co-stimulatory signals if activated by a self antigen => this is to have functioning B-cell receptors that are not self-reactive (or else auto-immune disease)
What is junctional diversity?
Random nucleotides added between the junctions of the VDJ arrangements to add even more diversity (non-DNA encoded, contrary to VDJ rearrangement)
What is the difference between the primary and secondary humoral immune responses?
Primary immune response: slow immune response, IgM is first antibody to respond, IgG comes later in small amount
Secondary immune response: fast immune response, IgG is first antibody to respond in high amounts, IgM appears later on
=> IgG has a higher affinity to the antigen than IgM
What reactions happen in the germinal center after the primary response?
Naïve B-cell goes to the germinal center (secondary lymphoid tissues) after an antigen has been presented by the help of an helper T-cell
Clonal expansion of B-cell happens, all B-cells have the same VDJ arrangement but have different little mutations (somatic hyper-mutations dependent of AID enzyme)
B-cells with the highest affinity are selected to produce the antibodies
Differentiation in antibody producing B-cells (plasma cells) and memory B-cells
After a germinal center reaction, which B-cell play an important role during a secondary response?
After the germinal center reaction, memory B-cell will produce the highest affinity antibodies against the pathogen
What is a UCA?
UCA = Un-mutated Common
Ancestor
(original naïve B cell before clonal expansion)
Why are B-cells much faster to respond after a germinal center reaction?
Memory B-cells act faster to mature into antibody-producing cells compared to a naïve B-cell which needs more co-stimulatory signals for this transformation to happen
Memory B-cells are long lasting, naïve B-cells are replenished every 7-14 days but memory B cells can persist for years
What are the 4 effector functions of antibodies?
- Neutralization of microbe and toxins
- Opsonization and phagocytosis of microbes (mainly for macrophages)
- Antibody-dependent cellular cytotoxicity (for NK cells)
- Complement activation (lysis of microbes, phagocytosis of microbes opsonized with complements fragments and inflammation)
Where do naïve B-cells reside?
Naïve mature B cells reside in the periphery in secondary lymphoid organs together with T helper cells
At the end, what does germinal centers produce?
Germinal centers produce high affinity memory B-cells and antibody-producing plasma cells that can provide sterilizing immunity upon re-challenge of the pathogen (this is how vaccines work)
