Celebrating More Than a Century of Research on Antibodies: Affirmation Through Negation via Complex Formation

Main Article Content

Neil S. Greenspan


In this brief commentary, I highlight the remarkable properties of antibodies (also known as immunoglobulins) revealed by more than 100 years of biomedical research. Since antibodies can be elicited through one or another means against almost any molecule or macromolecule, the universe of antibodies represents a sort of molecular mirror for the universe of molecules that make life possible. Consequently, as recounted below, antibodies play a role in almost every aspect of medicine and biomedical research.


Download data is not yet available.

Article Details

Author Biography

Neil S. Greenspan, Professor of Pathology at Case and the Director of the Histocompatibility and Immunogenetics Laboratory at University Hospitals Case Medical Center

Dr. Neil Greenspan received his A.B., magna cum laude, in Biochemical Sciences from Harvard College in 1975. He then earned M.D. and Ph.D. (Immunology) degrees at the University of Pennsylvania. From 1981 until 1986, Dr. Greenspan was a Resident in Laboratory Medicine (Clinical Pathology) at Barnes Hospital, and from 1982-1985 he was a Postdoctoral Fellow in Molecular Immunology at Washington University, both in St. Louis. In 1986, Dr. Greenspan became a faculty member at the Case School of Medicine. He is currently Professor of Pathology at Case and the Director of the Histocompatibility and Immunogenetics Laboratory at University Hospitals Case Medical Center.


1. Behring E, Kitasato S: Ueber das Zustandekommen der Diphtherie-Immunitat und der Tetanus-Immunitat bei thieren. Deutsche medizinsche Wochenschrift 1890; 16:1145-1148.

2. Emil von Behring - Biographical. Nobelprize.org: Nobel Media AB 2014; 2014 [cited 2017 March 13]. Available from: http://www.nobelprize.org/nobel_prizes/medicine/laureates/1901/behring-bio.html.

3. Schroeder HW Jr., Wald D, and Greenspan NS. Immunoglobulins: structure and function. In: Fundamental Immunology, Seventh Edition, Paul, William E. (Editor), Wolters Kluwer/Lippincott Williams and Wilkins, Philadelphia, 2012, pp. 129-149.

4. Hozumi N, Tonegawa S. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. Proc Natl Acad Sci U S A. 1976;73(10):3628-32. PubMed PMID: 824647. PubMed Central PMCID: PMC431171.

5. Weigert MG, Cesari IM, Yonkovich SJ, Cohn M. Variability in the lambda light chain sequences of mouse antibody. Nature. 1970;228(5276):1045-7. PubMed PMID: 5483159.

6. Murphy K, Travers P, and Walport M. Janeway’s Immunobiology, Seventh Edition, Garland Science, New York and London, 2008, p. 144.

7. Amit AG, Mariuzza RA, Phillips SE, Poljak RJ. Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science. 1986;233(4765):747-53. PubMed PMID: 2426778.

8. Davies DR, Cohen GH. Interactions of protein antigens with antibodies. Proc Natl Acad Sci U S A. 1996;93(1):7-12. Review. PubMed PMID: 8552677; PubMed Central PMCID: PMC: 40169.

9. Greenspan NS. Affinity, complementarity, cooperativity, and specificity in antibody recognition. Curr Top Microbiol Immunol. 2001;260:65-85. PubMed PMID: 11443882.

10. Greenspan NS, Cavacini LA. Chapter 14, Immunoglobulin function. In: Clinical Immunology: Principles and Practice, Fourth Edition, Rich, R.R. (Editor- in-Chief); Elsevier Saunders, Philadelphia, 2013, pp. 183-192.

11. Colvin RB, Smith RN. Antibody-mediated organ-allograft rejection. Nat Rev Immunol. 2005;5(10):807-17. PubMed PMID: 16175181.

12. Part 11: Diagnostic Immunology In: Clinical Immunology: Principles and Practice, Fourth Edition, Rich, R.R. (Editor-in-Chief); Elsevier Saunders, Philadelphia, 2013, pp. 1145-1201.

13. Terasaki PI, Bernoco D, Park MS, Ozturk G, Iwaki Y. Microdroplet testing for HLA-A, -B, -C, and -D antigens. The Phillip Levine Award Lecture. Am J Clin Pathol. 1978;69(2):103-20. Review. PubMed PMID: 75690.

14. Ujhelyi MR, Robert S. Pharmacokinetic aspects of digoxin-specific Fab therapy in the management of digitalis toxicity. Clin Pharmacokinet. 1995;28(6):483-93. Review. PubMed PMID: 7656506. doi: 10.2165/00003088-199528060-00006

15. Schanfield MS. Application of immunoglobulin heavy chain (GM, AM) and light chain (KM) allotypes to cases of disputed paternity. Exp Clin Immunogenet. 1989;6(1):112-22. PubMed PMID: 2629883.

16. Hendrickson JE, Delaney M. Hemolytic Disease of the Fetus and Newborn: Modern Practice and Future Investigations. Transfus Med Rev. 2016;30(4):159-64. PubMed PMID: 27397673. doi: 10.1016/j.tmrv.2016.05.008

17. Jetanalin P, Lee SJ, Kavanaugh A. Chapter 92, Biologic modifiers of inflammatory diseases. In: Clinical Immunology: Principles and Practice, Fourth Edition, Rich, R.R. (Editor-in-Chief); Elsevier Saunders, Philadelphia, 2013, pp. 1131-1142.

18. Yeung MY, Gabardi S, Sayegh MH. Use of polyclonal/monoclonal antibody therapies in transplantation. Expert Opin Biol Ther. 2017;17(3):339-352. PubMed PMID: 28092486. doi: 10.1080/14712598.2017.1283400

19. Bailly C, Cléry PF, Faivre-Chauvet A, Bourgeois M, Guérard F, Haddad F, Barbet J, Chérel M, Kraeber-Bodéré F, Carlier T, Bodet-Milin C. Immuno-PET for Clinical Theranostic Approaches. Int J Mol Sci. 2016;28;18(1). pii: E57. PubMed PMID: 28036044; PubMed Central PMCID: PMC5297692. doi: 10.3390/ijms18010057

20. Liao HX, Lynch R, Zhou T, Gao F, Alam SM, Boyd SD, Fire AZ, Roskin KM, Schramm CA, Zhang Z, Zhu J, Shapiro L; NISC Comparative Sequencing Program., Mullikin JC, Gnanakaran S, Hraber P, Wiehe K, Kelsoe G, Yang G, Xia SM, Montefiori DC, Parks R, Lloyd KE, Scearce RM, Soderberg KA, Cohen M, Kamanga G, Louder MK, Tran LM, Chen Y, Cai F, Chen S, Moquin S, Du X, Joyce MG, Srivatsan S, Zhang B, Zheng A, Shaw GM, Hahn BH, Kepler TB, Korber BT, Kwong PD, Mascola JR, Haynes BF. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 2013;496(7446):469-76. PubMed PMID: 23552890; PubMed Central PMCID: PMC3637846. doi: 10.1038/nature12053

21. Hawkins RE, Russell SJ, Winter G. Selection of phage antibodies by binding affinity. Mimicking affinity maturation. J Mol Biol. 1992;226(3):889-96. PubMed PMID: 1507232.

22. Hanes J, Jermutus L, Weber-Bornhauser S, Bosshard HR, Plückthun A. Ribosome display efficiently selects and evolves high-affinity antibodies in vitro from immune libraries. Proc Natl Acad Sci U S A. 1998;95(24):14130-5. PubMed PMID: 9826665; PubMed Central PMCID: PMC24338.