Assignment #10: Adaptive Immunity Flashcards
B cells arise in the bone marrow from what?
Progenitor Lymphoid Cells
Explain central tolerance, in reference to developing B cells
Selection processes occur that ensure that developing B cells that express receptors for self antigen, are inactivated or deleted.
what is the main purpose of B cell maturation?
central tolerance
B cell receptor complex includes what?
B cell antigen recognizing receptor (BCR) and associated heterodimers CD79a/CD79b
what is the role of the B cell receptor (BCR)?
cell surface membrane immunoglobulin (mIg) that recognizes and interacts with intact antigens
Is the BCR linked to any signal transduction pathways?
NO (remember its a cell surface membrane immunoglobulin)
what does link the BCR to the signal transduction pathway then?
CD79a/CD79b (Igalpha-Igbeta)
All naive (mature) B cells express, what two mIg isotypes?
IgM and IgD
Immunoglobulin (mIg) molecules are composed of what?
two identical heavy chains and two identical light chains linked by a disulfide bond. With each chain made up of a variable and constant region.
In mature (naive) B cells, what are the heavy chain and light chain constant regions made up of?
Heavy Chain –> Mu and Delta
Light Chain –> Kappa and Lambda
what segments are the heavy and light chains made up of?
Heavy –> V,D,J
Light –> V and J
Exquisite specificity (and hence diversity) is made possible because of what?
the V,D, and J gene segments, which encode the variable regions, are present on multiple germline genes that are rearranged to make unique variable regions.
Somatic recombination (construction of unique variable regions) is a result of 4 things.
- Multiple copies of germline V,D,and J gene
- Junctional diversity (due to the addition or deletion of bases)
- Random selection and combination of V,D, and J gene segments
- Random Assortment of light and heavy chains
The process in which DNA in the loci that encode the variable regions is cut and recombined to make an intact gene for the variable regions of the light and heavy chains is….?
Somatic recombination
What then triggers this somatic recombination process?
Activation of recombinases, which are the nuceloprotein products of the RAG-1 and RAG-2 genes
Explain what combinational diversity is
Random selection of V, D and J gene segments
Explain what junctional diversity is?
Additional DNA nucleotides may be deleted, or inserted at V,D,J gene segment junctions in order to maintain (downstream) an open reading frame
Incorporation of nucleotides at junctions is mediated by a template independent DNA polymerase, called?
terminal deoxynucleotidyl transferase (Tdt)
Explain what random association/assortment is
light chain with any heavy chain allows for another level of diversity in creating unique antigen binding sites
What is allelic exclusion?
Successful rearrangement of a heavy chain variable region from one chromosome inhibits the somatic recombination of the heavy chain variable region on the other member of the chromosome pair .
what is the net effect of allelic exclusion?
all mIg present on the surface of any one B cell will have the same heavy chain variable region.
In general when does B cell differentiation in the bone marrow occur?
Prior to any exposure to foreign antigens
In general what is B cell differentiation?
expression and silencing of distinct sets of genes at discrete stages of development.
What is the ultimate goal of B cell differentiation?
generation of B cell receptor that is non autoreactive.
