Standardized IMGT® Nomenclature of Salmonidae IGH Genes, the Paradigm of Atlantic Salmon and Rainbow Trout: From Genomics to Repertoires.

Susana Magadan,Ben F Koop,Oriol Sunyer,Stanislas Mondot,Aleksei Krasnov,Saida Hadi-Saljoqi,Rosario Castro,John Hansen,Irene Salinas,Sergey Afanasyev,Pierre Boudinot,Marie-Paule Lefranc,Delphine Lallias

doi:10.3389/fimmu.2019.02541

Abstract

In teleost fish as in mammals, humoral adaptive immunity is based on B lymphocytes expressing highly diverse immunoglobulins (IG). During B cell differentiation, IG loci are subjected to genomic rearrangements of V, D, and J genes, producing a unique antigen receptor expressed on the surface of each lymphocyte. During the course of an immune response to infections or immunizations, B cell clones specific of epitopes from the immunogen are expanded and activated, leading to production of specific antibodies. Among teleost fish, salmonids comprise key species for aquaculture. Rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) are especially important from a commercial point of view and have emerged as critical models for fish immunology. The growing interest to capture accurate and comprehensive antibody responses against common pathogens and vaccines has resulted in recent efforts to sequence the IG repertoire in these species. In this context, a unified and standardized nomenclature of salmonid IG heavy chain (IGH) genes is urgently required, to improve accuracy of annotation of adaptive immune receptor repertoire dataset generated by high-throughput sequencing (AIRRseq) and facilitate comparisons between studies and species. Interestingly, the assembly of salmonids IGH genomic sequences is challenging due to the presence of two large size duplicated IGH loci and high numbers of IG genes and pseudogenes. We used data available for Atlantic salmon to establish an IMGT standardized nomenclature of IGH genes in this species and then applied the IMGT rules to the rainbow trout IGH loci to set up a nomenclature, which takes into account the specificities of Salmonid loci. This unique, consistent nomenclature for Salmonid IGH genes was then used to construct IMGT sequence reference directories allowing accurate annotation of AIRRseq data. The complex issues raised by the genetic diversity of salmon and trout strains are discussed in the context of IG repertoire annotation.

Highlights

Vertebrate species with jaws (Gnasthostomata) that appeared more than 400 million years ago are all characterized by an adaptive immune system based on B and T cells along with the huge diversity and specificity of their antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR), respectively [1, 2]
The complete and correct assembly of the Salmonidae IGH loci is a significant challenge owing to (i) the existence of two duplicated loci due to the tetraploidization, (ii) the large size of each locus, (iii) the high number of different IGH variable (IGHV) subgroups compared to mammals, (iv) the internal amplification and potential gene conversion that occurred inside each locus during their evolution, and (v) the very high number of pseudogenes, many of them partial, relative to the functional genes
The IGH data published for Atlantic salmon [16], largely based on bacterial artificial chromosomes (BAC) sequencing, were used as a prototype for establishing the standardized IMGT nomenclature for salmonids and for dealing, by comparison, with newly identified IGH genes from both Atlantic salmon and rainbow trout genome assemblies

Summary

Introduction

Vertebrate species with jaws (Gnasthostomata) that appeared more than 400 million years ago are all characterized by an adaptive immune system based on B and T cells along with the huge diversity and specificity of their antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR), respectively [1, 2]. The analysis of the germline IGH locus defines the genomic repertoire with the identification of the functional variable (V), diversity (D), and joining (J) genes that participate in the synthesis of VH domains It allows the identification of the functional constant (C) genes that encode the constant regions of the heavy chains and define their isotypes [3,4,5,6,7]. Antibodies constitute a key factor for fish specific immunity and for the protection afforded by vaccines. As key species in aquaculture, Salmonids (family Salmonidae) including rainbow trout (Oncorhynchus mykiss; Oncmyk) and Atlantic salmon (Salmo salar; Salsal) constitute important models for the study of antibodies and B cell responses in fish

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Conclusion