Antibody Genetics I Flashcards
Where are B cells derived from in adult mammals?
Bone marrow
Where do B cells originally develop?
In foetal liver at 8-9 weeks gestation
What cells line the bone endosteum?
Progenitor cells
What do stromal reticular cells do?
Produce IL-7 to sustain B cell differentiation
Support B cell development
How many progeny can be produced by each progenitor?
64
What happen to the progeny?
They migrate to the centre of spongy bone
Adventitial reticular cells aid egress to the venous sinusoid then out into circulation
What percentage of B cells do not make it out of the bone?
75%
What happens to the B cells that do not leave the bone?
Apoptosis or phagocytosis by macrophages
What allows survival of B cells after selection?
Successful rearrangement of Ig gene (BCR)
How are autoreactive B cells removed?
By negative selection
What was Ehrlich’s side-chain theory?
That each B cell had multiple specificities (side chains)
What are the mechanisms of diversity?
Somatic recombination and somatic mutation
What does somatic recombination allow?
Joining of one segment of the gene to another
What does somatic mutation allow?
Sloppy joining of the gene segments
What happens when there is somatic recombination and mutation together?
Generate heavy and light chains of Ig
Pairing of unique heavy and light chains add diversity
What is the order of diversity generation?
First heavy chain rearranged
If successful then kappa light chain rearranges
If no kappa chain then lambda chain rearranges
What chromosome are the VDJ heavy chain segments on?
Chromosome 14
How is the functional heavy chain VDJ region formed?
Recombination of any one V with any one D and any one J
What does each V region code for?
A single peptide which directs the polypeptide to the RER, golgi and the out the cell