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Anergy in self-directed B lymphocytes: A statistical mechanics perspective
Elena Agliari1, Adriano Barra1, Gino Del Ferraro2
1Dipartimento di Fisica, Sapienza Università di Roma, P.le A. Moro 2, 00185 Roma, Italy.
Journal of Theoretical Biology
|May 17, 2014
Summary
Self-reactive B-cells remain harmless through clonal anergy. Statistical mechanics show this anergy is explained by the cognate response model, integrating Varela theory and explaining repertoire architecture.
Area of Science:
- Immunology
- Computational Biology
- Theoretical Biology
Background:
- Self-directed lymphocytes can evade deletion but remain harmless via clonal anergy.
- Two models explain B-lymphocyte anergy: Varela theory (repertoire orchestration) and cognate response model (lack of helper signaling).
Purpose of the Study:
- To reconcile Varela theory with the cognate response model for B-cell anergy.
- To investigate the emergence of B-repertoire architecture through ontogenetic learning.
Main Methods:
- Statistical mechanics modeling.
- Analysis of B-cell repertoire interactions within the idiotypic network.
Main Results:
- Helpers do not activate B-cells broadly interacting in the idiotypic network, supporting the cognate response model.
- Varela theory's concepts are reabsorbed into the cognate response framework.
- B-repertoire architecture, with highly connected self-directed clones, emerges from ontogenetic learning.
Conclusions:
- The cognate response model comprehensively explains B-cell clonal anergy.
- B-cell repertoire self-organization is a natural outcome of developmental processes.
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