Abstract
During a primary immune response, hundreds of naive T cells undergo clonal expansion. While some proliferate extensively and dominate the response, others cease division early, forming only small progeny families. Using a division-tracing experimental system, we found that secondary immune responses primarily originate from these small families, whereas large families contribute minimally. To explain this paradox, we developed mathematical models that provide quantitative and mechanistic insights. Our analysis reveals that rare stochastic "dropout" events —where individual cells exit expansion early— are key drivers of robust secondary responses. These "dropouts" differ from the vast majority of "conventional" memory cells formed during and after an immune response.

Biosketch

Rob de Boer uses mathematical and computational models to study the immune system in a quantitative manner. At Utrecht University, his research group focuses on quantifying the processes that shape immune dynamics — including the division rates and life spans of key immune cell types, the capacity of killer cells to eliminate target cells, and the diversity of naive and memory T-cell repertoires in both mice and humans. A central goal of his work is to understand how acute immune responses to viral and bacterial infections give rise to long-term immune memory, and how this memory is maintained throughout life.  See http://tbb.bio.uu.nl/rdb for a list of publications.