(03) Antibody Diveristy and B Cell Developement Flashcards
What does antibody repertiore refer to?
Complete collection of B cell receptor specificities that exists in the secondary lymphoid tissues of the host
What process is responsible for generating the 10^11 unique specificities of B cells?
- Genes that mediate this process
Somatic Recombination
- RAG-1 and RAG-2 (Recombination Activation Genes) mediate somatic Recombination
What are the light chain coding regions composed of?
- what are the 2 sets of light gene segments, that contain each of these 3 parts?
- Single Variable Gene Segment
- Single Joining Gene Segment
- Single Constant Gene Segments
**Kappa and Lambda
What are the heavy chain coding regions composed of?
- are there 2 sets of gene segments coding?
- Single Variable Region (V)
- Single Diversity Region (D)
- Single Joining (J) segment
- Single Constant (C) region
Where are the light and heavy chain genes located in the genome?
Lambda Light Genes = Chromosome 22
Kappa Light Genes = Chromosome 2
Heavy Chain genes = Chromosome 14
- *What do RAG-1 and RAG-2 do?
- what happens if you don’t have these enzymes?
Catalyze double stranded breaks and recombination events that make V-D and V-D-J recombinations
Lack of Enzymes = SCID (severe combined immunodeficiency)
- *What does TdT do?
- what processes is involved in?
- why is this important?
Catalyzes the addition of “N” nucleotides in the junctions between rearranging gene segments during somatic recombination
Processes:
- HEAVY CHAIN somatic recombination
- ß-chain rearrangements in T-cells
Importance:
- changes in the coding region cause even more variability in the number of specificities
T or F: any light chain produced can be paired with any heavy chain produced
True
T or F: somatic recombination is antigen dependent
False, this process occurs regardless of the presence of antigens
What are the two antigen dependent mechanisms of B cell development?
- Affinity Maturation (binding diversity)
- aka somatic hypermutation - Class Switching (functional Diversity)
What is somatic hypermutation?
- steps that lead to it?
- Where does it occur?
- B Cell Receives activation stimuli and begins to proliferate
- High rates of mutation occur IN RECOMBINED regions during proliferation
- Some mutated antibodies have higher affinity and some lower
Location:
- Germinal Center of B cell follicles of 2˚ lymphoid tissues
T or F: a POSITIVE selection method is used in affinity maturation/somatic hypermutation?
True, higher affinity cells are positively selected
What is the general outcome of somatic hypermutation?
The immune response improves over the course of the infection
T or F: all B cell initially produce IgE antibodies.
False, they produce IgM antibodies
What does class (isotype) switching do?
- Why is this efficient?
Changes the constant region of the antibody WITHOUT changes the variable region
THIS CHANGES FUNCTIONALITY NOT SPECIFICITY
- ONLY 1 B cell needs to be activated and it can do class switching to make IgG, IgE, IgA antibodies etc.
What is the order of constant regions?
- IgM
- IgD
- IgG3
- IgG1
- IgA1
- IgG2
- IgG4
- IgE
- IgA2
MD. GGAGGEA
What enzyme is required for both Class Switching AND for Somatic Hypermutation?
- what does an enzymes deficiency in this cause?
- Deficiency in which process is more detrimental?
AID - Activation-Induced Cytidine Deaminase
Causes:
- Hyper IgM syndrome
- Patients are susceptible to bacteria, fungi, and parasites as well as some viral pathogens such as the Flu
**Problem results from failure of Class switch NOT Hypermutation
Somatic Recombination
- 2 factors that cause variation
- dependency on antigen
Variation caused by:
- Imprecise end joining
- random combos of heavy and light chains
*Antigen Independent
Class Switching
- What does it allow for
- dependency on antigen
Allows immune system to pick the best antibody for the invading pathogen
*Antigen Dependent
Somatic Hypermutation
- purpose
- dependency on antigen
Allows for fine tuning of antibodies
*Antigen Dependent
Which of the following affect specificity and which affect functionality?
- somatic recombination
- somatic hypermutation
- class switching
Specificity
- somatic recombination
- somatic hypermutation
Functionality - class switching
IL-7 (interleukin-7) what cell type makes these?
- what cell receives?
- why are they needed?
- what happens if no IL-7 or IL-7 receptors are absent?
IL-7
Made by:
- Stromal Cells in Bone Marrow
Received by:
- B-cells
Need:
-Critical to growth and development of B-cells
No IL-7 or IL-7 receptors then patients have a normal amount of B-cells but they’re ineffective
T or F: immature B cells already have IgM on their surface
True, this means they have already rearranged their heavy and light chain genes
What is BTK and what is it needed for?
- what happens if you lack this enzyme?
BTK = Bruton’s Tyrosine Kinase
- Needed for proper signal transduction from surface receptors during B cell development
NO BTK = very few B-cells
Allelic Exclusion
- what is it
- How it works
- Only 1 chromosome is worked on at a time
If chromosome 14a fails it will move to chromosome 14b for a heavy chain gene
If chromosome 2a kappa fails then chromosome 2b kappa will be used
If these fail it will move to Lamba
What would happen if B cells that bound host antigens were not killed?
Autoimmune disease
What are the 4 possibilities of what can happen to a B-cell when it is allowed to interact with self antigens?
- Binds Self Antigens
- Apoptosis - Binds tightly to soluble molecules
- becomes anergic (unresponsive to antigenic stimuli) and DIES - Binds weakly to self Antigens
- migrates to periphery - Doesn’t bind anything
- migrates to periphery
What binds the Fc region of antibodies?
- Phagocytes
2. Complement proteins
