eBriefing

Immune Memory in Action: Modeling Affinity Maturation

Immune Memory in Action
Reported by
John Galbraith Simmons

Posted March 30, 2007

Overview

The random nature and magnitude of clonal selection provides computational biology and bioinformatics with rich prospects for illuminating fundamental conundrums in immunology. Drawing on experimental work in immune system biodynamics, Steven Kleinstein of Yale University School of Medicine offered a new perspective on the lymphocyte learning process known as affinity maturation.

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Articles

Jacob J, Kelsoe G. 1992. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers. J. Exp. Med. 176: 679-687. (PDF, 1.75 MB) FULL TEXT

Jacob J, Kelsoe G, Rajewsky K, Weiss U. 1991. Intraclonal generation of antibody mutants in germinal centres. Nature 354: 389-392.

Jacob J, Przylepa J, Miller C, Kelsoe G. 2007. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells. J. Exp. Med. 178: 1293-1307. (PDF, 1.16 MB) FULL TEXT

Kleinstein SH, Louzoun Y, Shlomchik MJ. 2003. Estimating hypermutation rates from clonal tree data. J. Immunol. 171: 4639-4649. FULL TEXT

MacLennan IC. 2005. Germinal centers still hold secrets. Immunity 22: 656-657. FULL TEXT

Magori-Cohen R, Louzoun Y, Kleinstein SH. 2006. Mutation parameters from DNA sequence data using graph theoretic measures on lineage trees. Bioinformatics 22: e332-e340. (PDF, 246 KB) FULL TEXT

Oprea M, Perelson AS. 1997. Somatic mutation leads to efficient affinity maturation when centrocytes recycle back to centroblasts. J. Immunol. 158: 5155-5162.

Radmacher MD, Kelsoe G, Kepler TB. 1998. Predicted and inferred waiting times for key mutations in the germinal centre reaction: evidence for stochasticity in selection. Immunol. Cell Biol. 76: 373-381.

William J, Euler C, Christensen S, Shlomchik MJ. 2002. Evolution of autoantibody responses via somatic hypermutation outside of germinal centers. Science 297: 2066-2070.

Speaker

Steven H. Kleinstein, PhD

Yale University School of Medicine
e-mail | web site | publications

Steven Kleinstein is an assistant professor of pathology at the Yale University School of Medicine. The focus of his research is the development and application of computational methods that leverage mathematical/statistical models and numerical simulations to improve understanding of experimental and clinical data. Detailing the immune response is a particular focus of his work. Kleinstein received his PhD in computer science from Princeton University in 2002.


John Galbraith Simmons

John Galbraith Simmons is a nonfiction author, novelist, and journalist who writes about science and medicine for popular and professional audiences. He is the author of The Scientific 100, which profiles one hundred of the most influential scientists in history, and Doctors and Discoveries: Lives that Created Today's Medicine.