Affinity Inequality among Serum Antibodies That Originate in Lymphoid Germinal Centers
Author(s)Eisen, Ellen A.; Chakraborty, Arup K.; Eisen, Herman N.; Kang, Myung Sun; Eisen, Timothy Jonas
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Upon natural infection with pathogens or vaccination, antibodies are produced by a process called affinity maturation. As affinity maturation ensues, average affinity values between an antibody and ligand increase with time. Purified antibodies isolated from serum are invariably heterogeneous with respect to their affinity for the ligands they bind, whether macromolecular antigens or haptens (low molecular weight approximations of epitopes on antigens). However, less is known about how the extent of this heterogeneity evolves with time during affinity maturation. To shed light on this issue, we have taken advantage of previously published data from Eisen and Siskind (1964). Using the ratio of the strongest to the weakest binding subsets as a metric of heterogeneity (or affinity inequality), we analyzed antibodies isolated from individual serum samples. The ratios were initially as high as 50-fold, and decreased over a few weeks after a single injection of small antigen doses to around unity. This decrease in the effective heterogeneity of antibody affinities with time is consistent with Darwinian evolution in the strong selection limit. By contrast, neither the average affinity nor the heterogeneity evolves much with time for high doses of antigen, as competition between clones of the same affinity is minimal.
DepartmentInstitute for Medical Engineering and Science; David H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Chemistry; Massachusetts Institute of Technology. Department of Physics; Ragon Institute of MGH, MIT and Harvard; Whitehead Institute for Biomedical Research
Public Library of Science
Kang, Myungsun, Timothy J. Eisen, Ellen A. Eisen, Arup K. Chakraborty, and Herman N. Eisen. “Affinity Inequality Among Serum Antibodies That Originate in Lymphoid Germinal Centers.” Edited by Sebastian D. Fugmann. PLoS ONE 10, no. 10 (October 7, 2015): e0139222.
Final published version