B Cell Development and Primary Ab Repertoire Flashcards
Early Pro- B cell
Heavy Chain D-J rearranging
Surface Ig absent
Late pro-B cell
Heavy Chain V-DJ rearranging
Surface Ig Absent
Large pre-B cell
Heavy Chain VDJ rearranged
M chain has a surrogate light chain that transiently takes it to the surface of pre-B-cell receptor.
Gets a signal to prevent further rearrangements
Stem Cell
CD34+
has no rearrangements.
Small pre-B cell
Light Chain V-J rearranging
Intracellular M chain is present
Immature B Cell
Assembly of IgM and IgM is expressed on the cell surface.
Called immature because they do not proliferate or differentiate in response to antigens.
Once it produces a specific Heavy or light chain containing a specific V region, it cannot produce another Ig that has a different V region.
Immature B cells come out into the periphery
Mature B-cell
B cells continue to mature in the periphery.
They express both membrane IgM and IgD with the original light chain. They both have the same V region.
Allelic exclusion
Each B cell can only be specific for one single antigen so it is necessary to make one of the alleles not functional.
Only one heavy and one light chain allele are productively rearranged.
Only one allele in a cell is expressed.
Ig gene rearrangement
Recombination signal sequence (RSS) are on the 3’ end of the V gene and the 5’ end of the J gene for the light chain and on the both sides of the D gene.
In a light chain each RSS next to the V gene recognizes a complement RSS next to the J gene. RAG1 & RAG2 recognize these and align the two RSS and cleave the DNA in between the exons and the RSS. This makes BREC (B-cell recombination excision circle). When a person is successfully making B-cells, they have BREC’s in the bone marrow. Show’s successful bone marrow transplants.
DNA ligase then ligates the two exons together.
Membrane IgM vs. Secreted IgM
Membrane and secreted IgM result from alternative RNA splicing. When there is splicing in the RNA, the transmembrane piece can either be included or excluded. If it is excluded, it will produce the secretory IgM.
IgM and IgD
Results from alternative splicing of primary transcripts.
The VDJ rearrangements are the same, but the expression of IgM and IgD results from alternative splicing that cuts out a constant region.
Junctional Diversity-N-region addition
N sequences (nucleotides) can be added to the junctions of REARRANGED VDJ genes during rearrangment.
Mediated by terminal deoxyribonucleotide transferase (TdT).
T-cell receptors
Have a Variant and Constant region and have Alpha and beta chains.
TCR vs Ig rearragment
V regions of alpha/gamma chains are encoded by VJ gene segments
C regions of alpha gamma chains are encoded by VDJ genes.
They rearrange by the same mechanism as Ig genes.
Only one VJ and VDJ rearrangment per cell.
