Genetic Basis of Ab structure / B lymphocyte biology - Shaw Flashcards
Where does B cell receptor differentiation take place?
Bone marrow
What are the two distinction functions of Ig, and the three subfunctions?
Two functions: antigen binding + effector functions
Three effector functions: Opsonization, neutralization, and complement activation
Why does IgE have an extra domain?
To bind to the receptors on granular immune cells of the myeloid line
What is affinity vs avidity?
Affinity - all noncovalent interactions between Ag and Ab, resulting in dissociation constant Kd
Avidity - apparent affinity, due to the fact that there are multiple binding sites and it would be difficult to dissociate all of them at the same time. Makes a much higher affinity Kd
Which light chain type rearranges first, and what is the net result of this in terms of circulating Ig?
Kappa locus rearranges first, and if successful, prevents lambda locus from rearranging (they are on separate chromosomes).
Result is there are about twice as many Kappa Ig molecules vs lambda
What do V, D, J, and C stand for? Which are not present in light chains?
V = variable D = diversity J = joining C = constant
Diversity segments are not present in light chains
In what type of B cell does heavy chain gene rearrangement take place, and what is the order?
Pro-B cell.
Heavy chains are spliced first. First the DJ regions on one chromosome are spliced, then a second splicing event in the Pre-B cell brings the V next to DJ.
A primary RNA transcript is made which contains VDJ, and constant regions for IgM and IgD. IgM heavy chain is initially translated.
What is allelic exclusion?
Once IgM heavy chain is successfully synthesized and paired with surrogate light chain, the IgM heavy chain prevents rearrangements of the other parental chromosome.
Attempt to make another heavy chain on the other chromosome will only commence once one fails.
What is the order of light chain rearrangement? What type of cell does it occur in?
Occurs in immature B cells
One light chain Kappa locus attempts to rearrange (VJ segments). If this fails, the other Kappa locus tries prior to the lambda locuses trying.
Allelic exclusion will occur once one is successful.
How are both IgM and IgD produced on the plasma cell with the same Ag specificity?
The heavy chain RNA transcript does alternative splicing to express the delta heavy chain as well. Since the VDJ regions are the same and only the constant region is the same, the same antigen can be recognized.
Both are expressed on the mature B cell
When and how does class switching occur?
After exposure to Ag, somatic rearrangement occurs non-reversibly at the DNA level in response to the cytokine environment (determines optimal Ig class).
What does a mature B cell become?
Either a memory B cell, which holds onto the antigen of interest on its membrane, or a plasma cell which starts secreting IgM (for instance) via RNA splicing
How does a plasma cell differ from a mature B cell? How is this controlled?
Plasma cells do not express antibodies as B cell receptors on their membrane
Membrane-anchoring versus secreted is controlled at the level of RNA splicing (Membrane anchor and secretion signals are always produced in the immature mRNA transcript)
What carries the signal that a successful heavy chain has been made, and light chain splicing should begin? What type of receptor is this?
Pre-B cell receptor shuts off surrogate light chain production and starts the light chain rearrangements, while also stopping heavy chain rearrangments.
This is a RTK which, if defective, will arrest all B cells in the pre-B stage (X-linked agammaglobinemia)
What is somatic hypermutation?
Process occurring after antigenic stimulation in mature B cells, does not occur in T cells.
Involves enzyme called Activation-induced deaminase which causes error-prone replication, potentially creating higher-affinity Ab’s via selective pressure.
