Abstract
In this paper we focus on the antigen-independent maturation of B-cells and, via statistical mechanics tools, we study the emergence of self/non-self discrimination by mature B lymphocytes. We consider only B lymphocytes: despite this is an oversimplification, it may help to highlight the role of B-B interactions otherwise shadowed by other mechanisms due to helper T-cell signalling. Within a framework for B-cell interactions recently introduced, we impose that, during ontogenesis, those lymphocytes, which strongly react with a previously stored set of antigens assumed as “self”, are killed. Hence, via numerical simulations we find that the resulting system of mature lymphocytes, i.e. those which have survived, shows anergy with respect to self-antigens, even in its mature life, that it to say, the learning process at ontogenesis develops a stable memory in the network. Moreover, when self-antigen are not assumed as purely random objects, which is a too strong simplification, but rather they are extracted from a biased probability distribution, mature lymphocytes displaying a higher weighted connectivity are also more affine with the set of self-antigens, ultimately conferring strong numerical evidence to the first postulate of autopoietic theories (e.g. Varela and Counthino approaches), according to which the most connected nodes in the idiotypic network are those self-directed.
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Notes
- 1.
We only stress here that there exist strong differences between B-cell maturation in the bone marrow and T-cell maturation in the thymus [7, 12, 13]. Unlike TCR (T cell receptor), that evolved to recognize characteristic patterns of pathogens, BCR (B cell receptor) is primarily diversified in random fashion and has not evolved to recognize a particular structure. Therefore each B cell can not discriminate self versus non self alone [9].
- 2.
Strictly speaking, negative selection requires that newborn lymphocytes also display a non-null binding strength with at least a self-antigen, probably to avoid antibodies completely cut off from the host [10].
- 3.
The string length is assumed to be the same for any antibody following the fact that the molecular weight for any immunoglobulin is accurately close to \(15\times 10^4\) [5].
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Agliari, E., Barra, A., Franz, S., Pentado-Sabetta, T. (2014). Some Thoughts on the Ontogenesis in B-Cell Immune Networks. In: Delitala, M., Ajmone Marsan, G. (eds) Managing Complexity, Reducing Perplexity. Springer Proceedings in Mathematics & Statistics, vol 67. Springer, Cham. https://doi.org/10.1007/978-3-319-03759-2_8
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