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Event Detail (Archived)

On Possible Indicators of Negative Selection in Germinal Centers

  • This event already took place in October 2024
  • Carson Family Auditorium (CRC)

Event Details

Type
Center for Studies in Physics and Biology Seminars
Speaker(s)
Bertrand Ottino-Loffler, Ph.D., fellow, Center for Studies in Physics and Biology, The Rockefeller University
Speaker bio(s)

A central feature of vertebrate immune response is affinity maturation, wherein antibody-producing B cells undergo evolutionary selection in microanatomical structures called germinal centers, which form in secondary lymphoid organs upon antigen exposure. While it has been shown that the median B cell affinity dependably increases over the course of maturation, the exact logic behind this evolution remains vague. Three potential selection methods include encouraging the reproduction of high affinity cells (“birth/positive selection”), encouraging cell death in low affinity cells (“death/negative selection”), and adjusting the mutation rate based on cell affinity (“mutational selection”). While all three forms of selection would lead to a net increase in affinity, different selection methods may lead to distinct statistical dynamics. We present a tractable model of selection and analyze proposed signatures of negative selection. Given the simplicity of the model, such signatures should be stronger here than in real systems. However, we find a number of intuitively appealing metrics — such as preferential ancestry ratios, terminal node counts, and mutation count skewness — require nuance to properly interpret.

Open to
Public
Contact
Melanie Lee
Phone
(212) 327-8636
Sponsor
Melanie Lee
(212) 327-8636
leem@rockefeller.edu


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