- #Antibody repertoire dominated by few clones Activator
- #Antibody repertoire dominated by few clones full
#Antibody repertoire dominated by few clones full
But, analysis of actual immune responses suggests that the full antibody repertoire size is not (and probably never has been) accessed since it is far in excess of the ability of elements in the immune system in both time and space to exploit it. 2 suggest that the cellular processes preexisted and were simply co-opted into the immune system, citing as an example the ancient origin of homologues of the complement system (e.g., the C3 molecule, a thioester-containing protein) in protostomes. 1Ī broader question, however, is whether repertoire diversification has run ahead of the cellular mechanisms by which such a diverse membership can be fully exploited.
#Antibody repertoire dominated by few clones Activator
The phylogenetic analysis of antibody genes since the divergence of the jawed vertebrates, in cartilaginous fish, bony fish, amphibians, reptiles, birds and mammals, and the absence of active recombinase activator genes RAG1 and RAG2 in jawless vertebrates suggests this to be the case. Unless the many pathogens present today have always existed, there should be evidence of increasing ‘fitness’ of antibody diversity and associated mechanisms over time. A critical question is whether the number of potentially dangerous pathogens on earth today has been a gradual accretion over millions of years and, pari passu, provided the driving force for the development of an adaptive immune system with an extensive antibody repertoire, or were they unconnected? The gradual accretion argument, while carrying a certain biological logic, may suffer from the teleological conundrum of the future requirements dictating the strategy of the past, particularly if the rate of pathogen diversification greatly exceeds the ability of the immune control systems to adapt by mutation at the same rate. It is currently thought that the antibody repertoire in the adaptive human immune system evolved to enable it to combat the massive number of foreign antigens derived from pathological bacteria, viruses, toxins, and the like. Finally, a solution that may reconcile the size difference anomaly, which is still a hot subject of debate, is suggested.
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. At the lower bound it could be questioned whether this is an insufficient repertoire size to counter all the potential antigen-bearing pathogens. There are questions that are relevant at both ends of this number spectrum. Estimates of the current size of the human antibody naïve 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. 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 naïve repertoire that then became more complex as combinatorial mechanisms were added. The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty.
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