Section: New Results

Modeling interfaces and contacts

Keywords: docking, scoring, interfaces, protein complexes, Voronoi diagrams, arrangements of balls.

Origin of Public Memory B Cell Clones in Fish After Antiviral Vaccination

Participants : F. Cazals, S. Marillet.

In collaboration with S. Magadan, L. Jouneau, S. Marillet, P. Boudinot (INRA, Virologie et Immunologie Moléculaires, Université Paris-Saclay, Jouy-en-Josas, France); M. Puelma Touzel, T. Mora, A. Walczak (Laboratoire de Physique Théorique, CNRS, Sorbonne Université, and Ecole Normale Supérieure (PSL), Paris, France); W. Chaara, A. Six (Sorbonne Université, INSERM, UMR S 959, Immunology-Immunopathology -Immunotherapy (I3), Paris, France); E. Quillet (INRA, Génétique Animale et Biologie Intégrative, Université Paris-Saclay, Jouy-en-Josas, France); O. Sunyer (Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States); S. Fillatreau (INEM, INSERM U1151/CNRS UMR8253, Institut Necker-Enfants Malades, Faculté de Médecine Paris Descartes, Paris, France; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique des Hopitaux de Paris (AP-HP), Hopital Necker Enfants Malades, Paris, France).

Vaccination induces public antibody clonotypes common to all individuals of a species, that may mediate universal protection against pathogens. Only few studies tried to trace back the origin of these public B-cell clones. Here [16] we used Illumina sequencing and computational modeling to unveil the mechanisms shaping the structure of the fish memory antibody response against an attenuated Viral Hemorrhagic Septicemia rhabdovirus. After vaccination, a persistent memory response with a public VH5JH5 IgM component was composed of dominant antibodies shared among all individuals. The rearrangement model showed that these public junctions occurred with high probability indicating that they were already favored before vaccination due to the recombination process, as shown in mammals. In addition, these clonotypes were in the naive repertoire associated with larger similarity classes, composed of junctions differing only at one or two positions by amino acids with comparable properties. The model showed that this property was due to selective processes exerted between the recombination and the naive repertoire. Finally, our results showed that public clonotypes greatly expanded after vaccination displayed several VDJ junctions differing only by one or two amino acids with similar properties, highlighting a convergent response. The fish public memory antibody response to a virus is therefore shaped at three levels: by recombination biases, by selection acting on the formation of the pre-vaccination repertoire, and by convergent selection of functionally similar clonotypes during the response. We also show that naive repertoires of IgM and IgT have different structures and sharing between individuals, due to selection biases. In sum, our comparative approach identifies three conserved features of the antibody repertoire associated with public memory responses. These features were already present in the last common ancestors of fish and mammals, while other characteristics may represent species-specific solutions.