Some thoughts on the ontogenesis in B-cell immune networks

TL;DR

This paper models B-cell immune network development using statistical mechanics, highlighting how ontogenesis influences self-tolerance and network connectivity, and demonstrating the emergence of anergy through numerical simulations.

Contribution

It introduces a thermodynamical framework combining ontogenesis and self-regulation in B-cell networks, emphasizing the role of negative selection in immune tolerance.

Findings

Self-reactive lymphocytes are eliminated during ontogenesis.

The model reproduces anergy in mature B-cell networks.

Connectivity distribution variance increases due to negative selection.

Abstract

We are interested in modeling theoretical immunology within a statistical mechanics flavor: focusing on the antigen-independent maturation process of B-cells, in this paper we try to revise the problem of self vs non-self discrimination by mature B lymphocytes. We consider only B lymphocytes: despite this is of course an oversimplification, however such a toy model may help to highlight features of their interactions otherwise shadowed by main driven mechanisms due to i.e. helper T-cell signalling. By analyzing possible influences of the ontogenesis of the immune system on the final behavior of B lymphocytes, we try to merge over the purely negative selection mechanism at their birth with the adult self-regulation process. The final goal is a "thermodynamical picture" by which both the scenarios can exist and, actually, be synergically complementary: Trough numerical simulations we impose on a recent scheme for B-cell interactions, that part of self-reactive lymphocytes are killed during the ontogenesis by which two observations stem: At first the so built system is able to show anergy with respect to the previously encountered self even in its mature life, then this naturally leads to an increasing variance (and average) in the connectivity distribution of the resulting idiotypic network. As a consequence, following Varela perspective, this shift may contribute to push to anergy those self-directed cells which are free to explore the body: identifying the latter as the highly connected ones, anergy is imposed even via the B-network regulation, and its strength is influenced by the negative selection.