3 Antibody Diversity and B Cell Development Flashcards
* Describe Sequence of Somatic Recombination * Describe the importance of * Affinty Maturation (somatic hypermutation) * Class Switching (Isotype Switching) * Describe B-Cell Development steps and tissues
What is a B cells purpose?
Make antibodies
Where are B cells made?
Bone Marrow
What is the terminal B cell differential cell that makes antibodies?
Plasma Cell
What is the long lived antigen specific cell ready to become an antibody producing cell?
Memory B Cell
What process in somatic recombination does not rely on antigen?
Somatic Recombination: Heavy and Light Chain Rearrangement
How is diversity in the B cell repertoire created?
Different gene splicing
Imprecise protein joining
Different protein pairing
What are light chain genes?
Kappa
Lambda
What chromosome is Kappa light chain gene found on?
Chromosome 2
What chromosome is Lambda light chain gene found on?
Chromosome 22
What regions do each Kappa and Lambda gene have?
V, J, Constant regions
What regions do heavy chain genes have?
V,D,J, C regions
How many heavy chain Constant gene alleles are there?
9, one for each Ig type
What brings the V,D, and J segments together?
DNA splicing
What brings the C region onto the VDJ or VJ segments?
RNA splicing
What do leader sequences do?
Direct Ig to:
Secrete
Membrane
How many alleles of each chain sub type are expressed?
Only 1, or the cell dies
What parts of B cell diversity creation are antigen dependent?
Somatic Hypermutation
Class Switching
Where does Somatic Hypermutation occur?
Secondary lymph
What does Somatic Hypermutation do?
Creates Affinity Maturation
What B cell undergoes Somatic Hypermutation and Class Switching?
Activated B cell
What are CDRs?
Complementary determining regions (hypervariable adaptive regions of Somatic Hypermutation Igs)
What B cell function relies on Helper T cells to occur?
Class Switching
What gene segment changes in class switching?
Constant (
* Vh exon associates with Ch genes to change the type of Constant region that will get expressed. This changes the type of Ig that is made.)
What Ig is made in every cell initially?
IgM
What Class Switch cannot occur?
IgM to IgD
What regions occur between V and C regions to allow class switching?
Switch regions
What enzyme allows class swithcing inside the DNA of B cells?
Switch recombinase
What cells do B cells depend on to live and grow?
Stromal Cells
Where do stromal cells live?
Bone Marrow
What is the overview of B cell development?
- Pro B cell
- Pre B cell
- Immature B cell
- Mature B cell
What is indicative of early Pro B cells?
DJ gene rearrangement
What is indicative of late Pro B cells?
V-DJ gene rearrangement
What is indicative of early Pre B cells?
m-chain expressed on surface
What is indicative of late Pre B cells?
V-J rearrangement
What is indicative of Immature B cells?
Clonal deletion of:
Anergics
Self Recognizers
What is indicative of Mature B cells?
Surface expression of:
IgM
IgD
What occurs if Mature B cells do not present IgM or IgD?
Apoptosis via CD8
What gene product allows double strand dna break and somatic recombination?
RAG 1
RAG 2
What enzyme allows the addition of N nucleotides at the junction of rearranged gene segments?
TdT
What is involved in surface receptor signal transduction? What disease does this lead to?
Bruton’s thymidine kinase (Btk)
X linked agammaglobulinemia
What enzyme allows class switching?
switch recombinase
What 3 things create self selection of B cells?
- self recognition of surface molecules
- self recognition of soluble molecules
- inability to bind antigen
What is vital to maturation of B cells?
Antigen!
What do B cells present to CD4?
MHC II : Antigen complex
What signal does CD4 send back to B cells to feedback for differentiation?
CD40L
What is the difference between membrane-bound Ab and secreted Ab?
Membrane is:
Monomeric
Transmembrane domain
Secretory and Membrane bound Ab pathways are allowed by:
RNA processing
