L3: Antibody Diversity/B cell development Flashcards
What is the first step in B cell development?
rearrange the Ig genes that code for the heavy and light chain that make up the Ig that is made by that B cell. IgM is then expressed on the surface of the B cell.
What is the first Ig that all B cells present?
IgM
What is the first type of Ab produced after B cells are activated?
pentameric IgM antibodies
True of False: each Ig molecule produced by any one B cell is identical.
True
What is the antibody repertoire?
The complete collection of antibody BCR specificities generated by somatic recombination
Does production of B cells in bone marrow depend on antigen presentation?
No. Somatic recombination is totally antigen-independent. They do not see antigens until they are in secondary lymph tissue
What do RAG-1 and RAG-2 do? What happens if you have a defect in either?
RAG-1 and RAG-2 are reactivation activation genes; enzymes that mediate somatic recombination. You will not be able to make functional lymphocytes.
How many Ig domains does each light chain have?
- One constant and one variable
How is heavy chain organization different from K light chains?
It has a D region in between the Variable region and J region.
Order: Variablle, D region, J region, Constant
Describe the organization of Lambda light chains.
Variable region, J region, Constant, J-region, constant, j region, constant
Describe the organization of K light chains?
variable, J region, constant
What is the first constant region in all Ig’s?
Mu chain, which codes for IgM, which is why it is always the first to be produced.
Which takes place first: light chain or heavy chain rearrangement?
Heavy chain rearrangement always occurs first in all developing B cells
What is the effect of only having one of each pair of chromosomes rearrange?
It ensures each B cell only codes for one specificity.
What segments are paired to make lambda and K light chains?
V and J segments
What segments are paired to give rise to heavy chains?
V, D, and J segments
Why is the imprecise nature of somatic recombination important?
Along with the recombination of heavy and light chains, it allows for massive variability from a handful of genes.
What percentage of B cells express antibodies that have both kappa and lambda light chains?
0%. B cells can only produce Abs with one specificity.
What is the order of heavy chains on Ig?
This WILL be on exam
Mu (IgM), delta (IgD), gamma3 (IgG3), gamma1 (IgG1), psuedo gene (nonfunct), A1 (IgA1), gamma2 (IgG2), gamma4 (IgG4), epsilon (IgE), A2 (IgA2)
Which is the only heavy chain region that doesnt have a switch region before it?
IgD
What is affinity maturation?
mutation that occurs at high frequency in the rearranged variable-region DNA of Ig genes in activated B cells, resulting in the production of varient antibodies, some of which have higher affinity for the antigen. Occures in follicles in secondary lymphoid tissues. B cells that express higher affinity Abs are positively selected. (antigen-dependent process)
What is IL-7 and what happens if it is defective?
It is a cytokine released from bone marrow stroma that is necessary for B cell production. Without it, it is impossible to develop a B cell repetoire
Describe the steps of Naive B cell production.
Lymphoid progenitor made in bone marrow; becomes early pro-B cell; D-J rearranging to make late pro-B cell; V-DJ rearranging to form Large pre-B cell; heavy chain translation and presentation of heavy chains;V-J rearranging of light chain; expression of IgM on surface; IgD starts to appear and cell is now a Mature B cell.
What is Bruton’s thymidine kinase (Btk)? What happens when it is deficient?
enzyme involved in signal transduction from cell-surface receptors during B cell development.
Without it, very small B-cell repertoire.
What enzyme(s) make double-stranded breaks in DNA during somatic recombination? What happens without them?
RAG-1 and RAG-2.
without them you wont have B or T cells
Which enzyme catalyzes the addition of N nucleotides at the junctions between rearranging gene segments?
TdT (terminal deoxynucleotidyl transferase)
What is AID? What type of Ig would you expect to be the most common in cells produced by an individual with a defect in AID?
activation-induced cytidine deaminase: enzyme that catalyzes class switching. It is also required for somatic hypermutation (Affinity maturation).
There would only be IgM because nothing would be able to class switch.
Where are most self-recognizing B cells found and terminated?
While they are still in the bone-marrow.
What does it mean for a cell to become anergic?
Its surface becomes dominated by IgD and has trouble reacting with anything. It quickly dies.
Which of the following DOES NOT contribute to the diversity of the B cell repertoire?
pairing of different light and heavy chains
isotype switching
somatic recombination
affinity maturation
imprecise DNA joining during somatic recombination
isotype switching. Just changes function of Ig, not specificity.
