title: Affinity Inequality among Serum Antibodies That Originate in Lymphoid Germinal Centers.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Myungsun
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Eisen
authors.affiliation: Environmental Health Sciences, School of Public Health, University of California, Berkeley, California, United States of America.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Eisen
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Ragon Institute of the Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Cambridge, Massachusetts, United States of America.
authors.forename: Arup K
authors.initials: AK
authors.lastname: Chakraborty
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Herman N
authors.initials: HN
authors.lastname: Eisen
mesh_terms: D000906:Antibodies / Q000097:blood* / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D006241:Haptens / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D012959:Socioeconomic Factors
chemical_list: D000906:Antibodies; D000939:Epitopes; D006241:Haptens