[HTML][HTML] Reconstructing a B-cell clonal lineage. I. Statistical inference of unobserved ancestors

TB Kepler - F1000Research, 2013 - ncbi.nlm.nih.gov
F1000Research, 2013ncbi.nlm.nih.gov
One of the key phenomena in the adaptive immune response to infection and immunization
is affinity maturation, during which antibody genes are mutated and selected, typically
resulting in a substantial increase in binding affinity to the eliciting antigen. Advances in
technology on several fronts have made it possible to clone large numbers of heavy-chain
light-chain pairs from individual B cells and thereby identify whole sets of clonally related
antibodies. These collections could provide the information necessary to reconstruct their …
Abstract
One of the key phenomena in the adaptive immune response to infection and immunization is affinity maturation, during which antibody genes are mutated and selected, typically resulting in a substantial increase in binding affinity to the eliciting antigen. Advances in technology on several fronts have made it possible to clone large numbers of heavy-chain light-chain pairs from individual B cells and thereby identify whole sets of clonally related antibodies. These collections could provide the information necessary to reconstruct their own history-the sequence of changes introduced into the lineage during the development of the clone-and to study affinity maturation in detail. But the success of such a program depends entirely on accurately inferring the founding ancestor and the other unobserved intermediates. Given a set of clonally related immunoglobulin V-region genes, the method described here allows one to compute the posterior distribution over their possible ancestors, thereby giving a thorough accounting of the uncertainty inherent in the reconstruction.
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