Jitt # 10 Activation-Induced Cytidine Deaminase Deficiency Flashcards
AID
Activation induced cytidine deaminase; converts cytidine to uridine by deaminating cytidine; triggers a DNA breakage and repair mechanism;
AID deficiency
caused by mutations in AID; causes hyper IgM syndrome;
AID deficiency symptoms
Increased susceptibility to recurrent pyogenic infections is the only symptom, similar to X-linked agammaglobulinemia
UNG
Uracil-DNA glycosylase; DNA repair enzyme involved in class switch recombination;
What two signals are required for AID protein production?
B cells produce AID when CD40R and IL-4 R (or other cytokine receptor?) are ligated by CD40L on T cells and IL-4 (Other cytokine?) binds
Cytidine
Cytosine bound to Ribose; transcription is upregulated after B cell/T cell interaction; causes the separation of Double stranded DNA; Cytidine is converted to uridine; which is recognized by UNG recognizes uridine and removes them; these sites (abasic/no base) are excised by DNA endonucleases creating DNA single stranded breaks.
What processes does AID play a role in?
Class switching and somatic hyper mutation of B cells.
Somatic hypermutation
The process by which B cells undergo expansion and increased affinity for antigens by the introduction of point mutations; occurs after antigen receptor and T cell receptor are engaged on B cells; selection then occurs
Affinity Maturation
The process by which B cells who have antigen receptors that have high affinity for antigen receive strong survival signals. Patients with AID cannot induce point mutations and do not undergo affinity maturation.
MMR
Mis-match repair; DNA repair mechanism; plays a primary role in detecting DNA mismatches during meiosis and class-switch recombination; recognizes U-G mismatches made by AID; produces double stranded breaks;
