IgM+ and IgT+ B Cell Traffic to the Heart during SAV Infection in Atlantic Salmon.

Anne Flore Bakke,Hege Lund,Petter Frost,Håvard Bjørgen,Preben Boysen,Sergey Afanasyev,Aleksei Krasnov,Erling Olaf Koppang

doi:10.3390/vaccines8030493

Abstract

B cells of teleost fish differentiate in the head kidney, and spleen, and either remain in the lymphatic organs or move to the blood and peripheral tissues. There is limited knowledge about piscine B cell traffic to sites of vaccination and infection and their functional roles at these sites. In this work, we examined the traffic of B cells in Atlantic salmon challenged with salmonid alphavirus (SAV). In situ hybridization (RNAScope) showed increased numbers of immunoglobin (Ig)M+ and IgT+ B cells in the heart in response to SAV challenge, with IgM+ B cells being most abundant. An increase in IgT+ B cells was also evident, indicating a role of IgT+ B cells in nonmucosal tissues and systemic viral infections. After infection, B cells were mainly found in the stratum spongiosum of the cardiac ventricle, colocalizing with virus-infected myocardial-like cells. From sequencing the variable region of IgM in the main target organ (heart) and comparing it with a major lymphatic organ (the spleen), co-occurrence in antibody repertoires indicated a transfer of B cells from the spleen to the heart, as well as earlier recruitment of B cells to the heart in vaccinated fish compared to those that were unvaccinated. Transcriptome analyses performed at 21 days post-challenge suggested higher expression of multiple mediators of inflammation and lymphocyte-specific genes in unvaccinated compared to vaccinated fish, in parallel with a massive suppression of genes involved in heart contraction, metabolism, and development of tissue. The adaptive responses to SAV in vaccinated salmon appeared to alleviate the disease. Altogether, these results suggest that migration of B cells from lymphatic organs to sites of infection is an important part of the adaptive immune response of Atlantic salmon to SAV.

Highlights

The adaptive immune system of modern bony fish includes B cells, which participate in specific targeting and elimination of pathogens
IgM+ and IgT+ B Cell Transcripts Increased in the Heart after Viral Challenge
In situ hybridization targeting IgM (Figure 1) and IgT (Figure 2) transcripts was performed on heart and pancreas/pyloric caeca samples collected at 0, 35, and 42 days post-challenge from unvaccinated fish

Summary

Introduction

The adaptive immune system of modern bony fish includes B cells, which participate in specific targeting and elimination of pathogens. Teleost B cells produce immunoglobulins (Ig) of three isotypes, i.e., IgM, IgD, and IgT (the latter being equivalent to IgZ in zebrafish) [1,2,3]. The level of IgT in serum of Atlantic salmon is 100–1000 times lower than the level of IgM [9]. The ratio of IgT to IgM in rainbow trout is much higher in mucus, and several studies have suggested a primary role of IgT in mucosal immunity of salmonid fish, especially after infection with parasites [11,12,13]. Pathogen-specific responses of IgT were shown to be present in the internal organs of rainbow trout, namely, the spleen [1] and kidney [14], after infection with viruses and parasites, respectively

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