Understanding the human antibody repertoire
Open Access
- 1 January 2020
- journal article
- review article
- Published by Informa UK Limited in mAbs
- Vol. 12 (1), 1729683
- https://doi.org/10.1080/19420862.2020.1729683
Abstract
The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty. Uncertainty in respect of whether the various elements have always served a specific defense function or whether they were co-opted from other organismal roles to form a crude naive repertoire that then became more complex as combinatorial mechanisms were added. Estimates of the current size of the human antibody naive repertoire are also widely debated with numbers anywhere from 10 million members, based on experimentally derived numbers, to in excess of one thousand trillion members or more, based on the different sequences derived from theoretical combinatorial calculations. There are questions that are relevant at both ends of this number spectrum. At the lower bound it could be questioned whether this is an insufficient repertoire size to counter all the potential antigen-bearing pathogens. At the upper bound the question is rather simpler: How can any individual interrogate such an astronomical number of antibody-bearing B cells in a timeframe that is meaningful? This review evaluates the evolutionary aspects of the adaptive immune system, the calculations that lead to the large repertoire estimates, some of the experimental evidence pointing to a more restricted repertoire whose variation appears to derive from convergent 'structure and specificity features', and includes a theoretical model that seems to support it. Finally, a solution that may reconcile the size difference anomaly, which is still a hot subject of debate, is suggested.Keywords
This publication has 80 references indexed in Scilit:
- The Restricted DH Gene Reading Frame Usage in the Expressed Human Antibody Repertoire Is Selected Based upon its Amino Acid ContentPublished by The American Association of Immunologists ,2013
- A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo1[S]Journal of Lipid Research, 2011
- Reference values for B cell subpopulations from infancy to adulthoodClinical and Experimental Immunology, 2010
- The origins of the Rag genes—From transposition to V(D)J recombinationSeminars in Immunology, 2010
- Precise determination of the diversity of a combinatorial antibody library gives insight into the human immunoglobulin repertoireProceedings of the National Academy of Sciences of the United States of America, 2009
- A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primatesProceedings of the National Academy of Sciences of the United States of America, 2009
- Large-scale analysis of human heavy chain V(D)J recombination patternsImmunome Research, 2008
- The road to TollNature Reviews Immunology, 2004
- Antibody-antigen Interactions: Contact Analysis and Binding Site TopographyJournal of Molecular Biology, 1996
- Shape Complementarity at Protein/Protein InterfacesJournal of Molecular Biology, 1993