Generation of antibody diversity Flashcards
How is antibody diversity reached:
Array of different antigen specificity is achieved by recombination of antibody genes during antigen independent differentiation of B-cells in bone marrow.
What are our 3 antibody genes?
2 light chain (kappa and lambda) and 1 heavy chain gene
How is the kappa-light chain gene segment organised in germline DNA?
Singal sequences preced each V gene segment and stop sequences follow the C-kappa gene segment.
V, J, C
What is V
Variable gene segment
What is J
Joining gene segment
What is C
Constant gene segment
What is D
Diversity gene segment
How is the heavy chains gene segment in germline DNA organised?
Each CH gene segment is made of several exons.
Singal leader sequences precede each V gene degment and stop sequences follow heavy chain gene segments.
V, D, J, C
When do Ig genes become functional?
When they are rearranged
When are Ig genes rearranged?
During antigen independent differentiation of B cells in the bone marrow.
What does each light chain use to generate the coding region of the variable domain?
One V and one J gene segment
What does each heavy chain use to generate the coding region of the variable domain?
One V, one D and one J segment
What is the process of Ig gene rearragment called?
V(D)J recombination
What are the basic principles of light chain gene recombination?
In germline DNA: somatic recombination VJ joining
In rearranged DNA of Pre-B-cell: Transcription
RNA splicing produces mRNA in the virgin B cell
Where is the light chain mRNA translated?
ER
Where do the light chains associate with the heavy chains to make an antibody?
ER
What are the basical principles of heavy chain gene recombination?
Germline DNA: Somatic recombination DJ joining: Then somatic recombination VDJ joining
In the rearranged DNA pre-B-cell: Transcription
Primary RNA transcript: RNA splicing
mRNA in virgin B cell
What is junctional diversity?
Where nucleotides are added/removed at random sites, V, D and J gene segments are recombined.
What does the D segment partially code for>
The 3rd CDR corresponding to the join between the V and J segment in the heavy chain.
What does junctional diversity increase>
Number of antigenic specificities
When do B cells switch Ig class?
As immune response matures.
What Ig do naive B-cells exiting the bone marrow express?
IgM and IgD on their cell surface.
What is the 1st Ig secreted in response to antigens?
IgM
As the humoural response matures B-cells undergo class switching, the Igs expressed are:
Either IgE, IgA or IgG instead of IgM/D.
