B cell development Flashcards
V region exons
300 bp sections at the 5’ end of each Ig locus that are separated by non-coding DNA
Joining segments
Downstream of the V region, they have additional coding sequences that are about 30-50 bp long
Diversity segments
Additional coding sequences present downstream of V and J regions, but ONLY IN HEAVY CHAINS
Location of C region genes
Varying distances in the 3’ direction from the V genes
How many exons are in the Ch region?
Three to four, plus another one for either the cytoplasmic/transmembrane domain
Ig genes are only expressed where?
In B cells
Heavy chain: DJ
The first Ig gene rearrangement occurs here; joins one D and one J segment and deletes intervening DNA
Heavy chain: VDJ
After DJ rearrangement, one of the many V genes is attached to the DJ complex. All segments 5’ to the DJ complex are deleted
What is significant about the VDJ rearrangement step?
Only happens in cells committed to be B cells, and it is a highly regulated step because V transcription begins right after deletion of the unused D segment
Light chain: VJ
VJ complex is formed in the light chain after complete VDJ rearrangement of the heavy chain.
When does transcription begin for the light chain?
When the C region is joined to the VJ complex
Formation of immature B cell
The kappa chain completed after light chain rearrangement joins with mu segment from heavy chain rearrangment, making IgM, which is then expressed on the cell surface
Major rule of antibody production
One B cell makes only one kind of antibody because of allelic exclusion
How does the B cell bypass the major rule of antibody production?
Alternative splicing after mRNA production
ProB cells
Precursor of PreB cells; have heavy chain DJ rearrangements and no light chain rearrangements
PreB cell
Earliest cell that produces mu heavy chain with variable and constant domains; only found in hematopoietic tissues.
What comprises a preB receptor?
Mu chains, surrogate light chains, Ig-alpha and Ig-beta
Immature B cell
Kappa or lambda light chains are now produced, associating with the previously made mu chains and expressing IgM on the surface
Cannot respond to antigens
Mature B cell
Complete Ig; migrate out into the periphery and can respond to antigens
How do B cell IgM and IgD respond to the same antigens?
They both have the same V region and therefore the same antigen specificity
Recognition sequences
DNA sequence that mediates the recombination of V, D, and J gene segments; located on either side of the D segments and after V or before J
RAG1 and RAG2
Recognize RSSes, loop them together, and excise them out, leaving just the exons that are joined by DNA ligase
Are all rearrangements functional?
No
BRECs
The excision loops that are left behind after RAG1/RAG2 activity. Clinically important for testing B cell proliferation after bone marrow transplants
TdT
Mediates random addition of new nucleotides added to the junctions during VDJ rearrangement
Junctional diversity by N-region addition
N sequences are added into the junctions during VDJ arrangement
What happens to B cells that have nonfunctioning VDJ?
They are deleted
What happens when B cells have anti-self reactivity?
Can become anergic, can be deleted, or can try and be salvaged by receptor editing
Receptor editing
When anti-self is detected, B cell maturation arrests and new combination is used. If that new specificity also is self-reactive, the cell is killed. If not, it can continue as a functional B cell
Most T cells have what type of receptors?
Alpha/beta receptors (5% have delta-gamma)
Functional structure of a T cell receptor
Has two alpha and two beta domains, variable domains on the periphery
