Diabetogenic B-lymphocyte activity may be enhanced by SHM induced increases in Ig antigen
affinity.
-SHM requires AID induced double strand DNA breaks repaired by RAD51 complex proteins.
-AID is expressed at higher levels in B-lymphocytes from NOD mice than control strains
-A small RAD51 blocking molecule specifically induces apoptosis of AID expressing B-lymphocytes
from both NOD mice and humans.
-RAD51 blockade is being tested as a new B-lymphocyte directed late disease stage T1D intervention
approach in NOD mice.
-For possible future clinical translation purposes it will be important to assess if diabetogenic Blymphocytes
in humans are undergoingAID induced SHM, and thus may be susceptible to depletion
by RAD51 blockade.
-To address this need nPOD is being requested to supply five cryopreserved PLN samples each from
T1D patients and controls.
-We will use these nPOD samples to determine if B-lymphocytes within PLNs of T1D patients express
higher AID levels than those from controls and thus more susceptible to RAD51 blockade induced
apoptotic death.
-Previous published work by Jax investigators demonstrate they have an ability to assess AID
expression by human B-lymphocytes, and determine their sensitivity to RAD51 blockade induced
apoptosis.