5 and 6- B Cell Dev. and Generation of Primary Antibody Repertoire Flashcards
Sequential rearrangements of ig genes in B cell precursors:
Stem cell, Early Pro B, Late Pro B, Large Pre B, Small Pre B, Immature B and Mature B cells
Allelic exclusion
Only one Vh and one Vl rearranged per B cell
The earliest B-cell type that synthesizes a detectable Ig gene product.
Pre-B lymphocytes.
Contain cytoplasmic mu chain.
Where do Mature B-cells go?
Having acquired a complete Ig and, therefore, an antigen specificity, B cells migrate out of the bone marrow and can be found in the peripheral circulation and lymphoid tissues.
What can be used clinically to determine if a patient is creating B-cells in the bone marrow?
The presence of BREC (B-cell recombination excision circle) aka leftovers of VDJ rearrangement.
How can mu and delta heavy chains be produced simultaneously by the same B cell, given that one cell makes only one antibody?
Mu and Delta chains with the same Vh domain result from alternative splicing of primary transcripts.
IgM and IgD on a given B-cell have the same…
Vh +Vl
Generation of Antibody Diversity (3 methods)
(1) Combinatorial Joining of V,D, and J segments in many different ways.
(2) Addition of nucleotides (n-sequences) by TdT, which were not present in germline.
(3) Different Combinations of H and L Chain Proteins
What happens to B cells with nonfunctional VDJ genes? B cells with anti-self reactivity?
(1) nonfunctional–> Deleted
(2) anti-self reactivity –> can become anergic, can be deleted, can be rescued by receptor editing
The overall organization of T Cell Receptor (TCR) genes is similar to that of…
Ig genes
Main differences between Mature and Immature B cells?
Imm. = IgM and in bone marrow
Mat. = IgM + IgD and in Periphery
What type of heavy chain do Pre-B cells have?
Mu Heavy chain
RAG 1 and RAG 2
Recognize complementary Recombination Signal Sequences (RSS) and cleave the DNA, bringing V, J and sometimes D segments together for ligation.
What often causes auto-immunity?
Activation of anergic B-cells
Which chain can receptor editing effect and why?
Only the LIGHT CHAIN because the alternative D segments which would be used to edit the heavy chain have already been deleted by this point. Therefore self-reactivity due to the heavy chain cannot be edited.
