Anergy in self-directed B lymphocytes: A statistical mechanics perspective.
Self-directed lymphocytes may evade clonal deletion at ontogenesis but still remain harmless due to a mechanism called clonal anergy. For B-lymphocytes, two major explanations for anergy developed over the last decades: according to Varela theory, anergy stems from a proper orchestration of the whole B-repertoire, such that self-reactive clones, due to intensive feed-back from other clones, display strong inertia when mounting a response. Conversely, according to the model of cognate response, self-reacting cells are not stimulated by helper lymphocytes and the absence of such signaling yields anergy. Through statistical mechanics we show that helpers do not prompt activation of a sub-group of B-cells: remarkably, the latter are just those broadly interacting in the idiotypic network. Hence Varela theory can finally be reabsorbed into the prevailing framework of the cognate response model. Further, we show how the B-repertoire architecture may emerge, where highly connected clones are self-directed as a natural consequence of ontogenetic learning.
Dipartimento di Fisica, Sapienza Università di Roma, P.le A. Moro 2, 00185 Roma, Italy.
Elena
E
Agliari
Dipartimento di Fisica, Sapienza Università di Roma, P.le A. Moro 2, 00185 Roma, Italy. Electronic address: adriano.barra@roma1.infn.it.
Adriano
A
Barra
Department of Computational Biology, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
Gino
G
Del Ferraro
Dipartimento di Fisica, Sapienza Università di Roma, P.le A. Moro 2, 00185 Roma, Italy.
Francesco
F
Guerra
Dipartimento di Matematica, Sapienza Università di Roma, P.le A. Moro 5, 00185 Roma, Italy.
Daniele
D
Tantari
D000465:Algorithms; D001402:B-Lymphocytes / Q000166:cytology*; D017635:Clonal Anergy; D003198:Computer Simulation; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D007107:Immune System; D007108:Immune Tolerance / Q000502:physiology*; D008954:Models, Biological; D015233:Models, Statistical; D013269:Stochastic Processes; D013601:T-Lymphocytes / Q000166:cytology
D000939:Epitopes
Immune networks; Lymphocyte homeostasis; Self–nonself-discrimination