(08) B cell development

Question 1

(Somatic Hypermutation)

1. When a b cell has been activated to proliferate (ag specific), and enzyme (called what?) chemically changes DNA bases to a different base, resulting in what?
2. This occurs with help of what and where?

Answer 1

1. activation induced deaminase; a new codon
2. T cell help; in germinal center in lymphoid tissue

Question 2

(Somatic Hypermutation cont)

1. If the mutation provides better binding of the Ab pocket to the Ag, what happens? What is the pocress called?
2. What happens if the binding is decreased?

Answer 2

1. these b cells are selected; affinity maturation
2. these b cells do not successfully compete for Ag and die via apoptosis

Question 3

(Somatic Hypermutation Mechanism)

1. What is the enzyme responsible for mutations in somatic hypermutation events?
2. What is the major change? What can this change?

Answer 3

1. activation-induced cytidine deaminases (AID)
2. conversion of cytidiine residue to a thymidine residue; the amino acid encoded

Question 4

1. Affinity maturation occurs only in response to what?
2. Where does this take place?
3. What is the end result?

Answer 4

1. antigen stimulation
2. within germinal centers in secondary lymphoid organs
3. increased antigen recognition and binding efficiency

Question 5

1. Somatic Hypermutation leads to _______ where the “quality” of the antibodies produced gradually increases.
2. This process occurs where during what?
3. An enyzme deaminates what and what in the VDJ and VJ region of the antibody gene? Causing what?
4. Does it occur on heavy chain or light chain?

Answer 5

1. affinity maturation
2. germinal center in secondary lymphoid organs during B cell proliferation
3. adenosines and cytosines; the wrong base to be incorporated when that stretch of DNA is copied
4. both

Question 6

(Somatic Hypermutation mechanism)

1. What is another way some species do to achieve the same thing as somatic hypermutation? What happens?
2. Which species use hypermutation exclusively?
3. Which use mostly gene conversion? Do they have a lot of variable region genes?
4. Which species use gene conversion during B cell differentiation, but hypermutation during an immune response?

Answer 6

1. Gene conversion; rather than repair by translesion syntehsis (as in hypermutation), gene conversion just inserts a gene segment
2. humans and mice
3. pigs, cattle, rabbits; no
4. chicken

Question 7

(Gene Conversion)

1. Which species exhibit little diversity in V, D, and J?
2. How is diversity in the binding pocket generated? explain it!
3. Does gene conversion occur with or without T cell stimulation?
4. Where does it occur in birds? in ruminants?

Answer 7

1. horses, rabbits, birds
2. gene converstion; short sequences within the exon are replaced by V gene segments from pseudogenes (genes that used to be functional at one point evolution)
3. without
4. bursa; Peyer’s patches

Question 8

1. A mature B cell traffics to what tissues?
2. If it encounters an Ag which fits into the Ab pocket, and receives T cell assistance - it will do what?
3. What occurs during this stage?
4. This B cell maturation leads to formation of what? which do what?

Answer 8

1. peripheral tissues (including secondary lymphoid organs)
2. proliferate to make many copies of itself
3. Somatic hypermutation
4. plasma cells; secrete large amounts of Ab (some will become memory cells)

Question 9

(Somatic Hypermutation vs. Isotype Switching)

1. Does switching from IgM to IgG affect the binding site?
2. Somatic hypermuation changes what?
3. Are these both occuring in germinal center?

Answer 9

1. no
2. the codon sequence in the VDJ, which changes the binding pocket
3. yes

Question 10

(Class (isotype) Switching)

1. Activated B cells will rearrange their somatic DNA to produce antibodies of a different isotype following what?
2. The switch only involves what region?
3. Does specificity of the B cell change?
4. What happens to the intervening DNA?
5. Do Light Chains switch classes?

Answer 10

1. appropriate stimulation by cytokines
2. the heavy chain constant region
3. no
4. is looped out and lost (preventing switching back)
5. no

Question 11

(Cytokine favorites)

1. Which isotype is favored by IL-4
2. IFN-gamma?
3. TGF-beta?
4. Can isotype switching more than once?
5. What is the order of isotype? Can you go back upstream?
   - when you have a large immune response against something like a worm - initial reaction produces - IL-4 - promotes IgE production - IgE activates mast cells an eosinophils which are good at fighting worms

Answer 11

1. IgG1, IgE
2. IgG2a, IgG3
3. IgA, IgG2b
4. yes
5. IgM (IgD), IgG, IgE, IgA; nope

Question 12

(Antibody Isotypes)

1. Isotype or class switching has a major impact on the immune response based on the properties of each isotype. Escpecially important for what?
2. Which isotypes are secreted by plasma cells in the spleen, lymph nodes, and bone marrow?
3. What is the major Ab isotype produced during a primary response?
4. Which can be surface bound or secreted as a pentamer?
5. Which is secreted by plasma cells found in tissues near body surfaces?
6. Which has an Fc portion that binds to receptors on mast cells and basophils?
7. Which one gets out on mucosal surfaces?
8. Which have longest half life in blood?

+ look at the table a little bit

Answer 12

1. phagocytes
2. IgG and IgM
3. IgM
4. IgM
5. IgA
6. IgE
7. IgA
8. IgG

Question 13

(Ab receptors)

1. Many immune cells express receptors thatn recognize the what on an antibody?
2. What does this interaction cause?
3. Is there a whole family of Fc receptors?
4. What does Fc stand for again?
5. Most Fc receptors bind which type?
6. Mast cells and eosinophils have receptors for which type?
7. IgG receptors are primarily on what?

Answer 13

1. the Fc region
2. activates the cell, including phagocytosis or expulsion of granules
3. yes
4. constant fragment
5. IgG1
6. IgE
7. phagocytes

Question 14

(Antibody Memory)

1. When the immune system again encounters antigen A, a more rapid and stronger Ab response occurs due to what?
2. The isotype will swith from what to what?
3. So if you have mostly IgM? Been around for awhile?

Answer 14

1. immunological memory
2. and IgM (primary response) response to IgG (more in secondary response)
3. early response; IgG

Question 15

(Immunological Memory)

1. When are these long-lived cells generated? Where distributed?
2. Have memory B cells usually undergone affinit maturation such that the binding to specific antigen is much greater in a second response to antigen?
3. Memory B cells reside where?

Answer 15

1. following initial exposure to and antigen; throughout secondary lymphoid tissue
2. yes
3. the bone MARROW

Question 16

(Role of Antibody in Host Defense)

• Antibodies participate in protecting host by doing what three things?

Answer 16

1. neutralization - prevents a toxin/virus/bacterium from binding to host cells
2. opsonization - facilitates pahocytosis of bacteria or particles and NK cell activation (ADCC)
3. Complement Activation - initiates complement cascade leading to cell lysis