Title: Estimating hypermutation rates during immune responses
Speaker: Steven Kleinstein, Princeton University
Date: Wednesday, May 26, 2004, 1:00 pm
Location: Hill Center, Room 260, Rutgers University, Busch Campus, Piscataway, NJ
Many immune responses are initiated through the binding of antibody receptors present on the surface of B cells. Once activated, these B cells can undergo a process of somatic hypermutation whereby point mutations are introduced into the DNA coding for their antibody receptor. These mutations can have important consequences for the affinity and specificity of the response.
To understand the mechanisms underlying the varying pattern of mutations that occur during immune and autoimmune responses, estimates of the somatic hypermutation rate are critical. However, despite its significance, precise estimates of the mutation rate do not currently exist. Microdissection studies of mutating B cell clones provide an opportunity to measure this rate more accurately than previously possible. Each microdissection experiment provides a number of clonally related sequences which, through the analysis of shared mutations, can be genealogically related to each other. The 'shape' of these clonal trees is influenced by many processes including the hypermutation rate. We have developed two different methods to estimate the mutation rate based on these data; one is numerical (based on a computer simulation of clonal expansion), while the other is analytical. In this talk I will describe these methods, as well as the results of applying them to both simulated and experimental data.
Seminar sponsored by DIMACS/BIOMAPS Seminar Series on Quantitative Biology and Epidemiology.