B cell development Flashcards
somatic recombination
DNA splicing for gene rearrangement for the variable region. For heavy chain DJ is joined first then V is joined to DJ. For light chain, V and J are joined. This is not reversible. Facilitated by RAG enzyme
RAG (recombinant activation gene)
binds to certain sequences and pulls ends together. produces coding joint (rearranged gene that is used for variable region) that is used and signal joint that is lost. Sloppy slicing so needs TdT and repair enzymes to clean up
TdT (terminal deoxy transferase)
only exists at certain points in cell life cycle, randomly assigns bases to free end of DNA, does not read off any template
N region
unpredictable region between D and J with random nucleotides. Part of junctional diversity
Heavy Chain Rearrangement
D-J rearrangements on both chromosomes, V-DJ rearrangement on first chromosome, V-DJ rearrangement on second chromosome (if first chromosome is unsuccessful)
Light Chain Rearrangment
Rearrange kappa gene on first chromosome, Rearrange kappa gene on second chromosome (if previous step unsuccessful), Rearrange lambda gene on first chromosome (if previous step unsuccessful), Rearrange lambda gene on second chromosome (if previous step unsuccessful)
What occurs between heavy and light chain rearrangment
tests heavy chain with surrogate light chain so that it can place heavy chain on cell surface
RNA splicing.
can result in class switching. can either result in expression of IgM or IgD or both. can go back and forth depending on state of B cell. can also determine if IgM is transmembrane or secreted.
Class switch
no RAG needed. DNA splicing. constant regions are brought together to form a different heavy chain (ex. IgG, IgE, IgA)
somatic hypermutation
takes place in the whole variable region, single random base changes, does not take place in the constant region or other parts of the B cell genome, targets rearranged gene segments encoding the variable region
does not take place in T cells, only B cells during time they are being stimulated by T cells, occurs at the same time with class switch
Activation-induced cytidine deaminase (AID)
enzyme responsible for both class switching and somatic hypermutation
T cell receptor gene rearrangement
all the same mechanisms as B cells except somatic hypermutation. still needs RAG and TdT.
what happens when you lack RAG
no T cells or B cells
what happens when you lack TdT
antibodies with lower affinities to antigens (no random mutations)
parts of lymph nodes that are active during B cell development
medullary cords: primary focus for expansion of antigen-activated B cells
primary follicle: secondary forcus for expansion of antigen activated B cells is in the germinal center
