Macrophage-B Cell Interactions in the Inverted Porcine Lymph Node and Their Response to Porcine Reproductive and Respiratory Syndrome Virus.

Elise Bordet,Olivier Bourry,Elisa Crisci,Nicolas Bertho,Stéphane Rault,Elisabetta Giuffra,Olivier Boulesteix,Edwige Bouguyon,Thibaut Larcher,Jérémy Pezant,Christelle Langevin,Maxence Frétaud,Isabelle Schwartz-Cornil,Mickael Bourge,Alexis Pleau,Patricia Renson

doi:10.3389/fimmu.2019.00953

Abstract

Swine lymph nodes (LN) present an inverted structure compared to mouse and human, with the afferent lymph diffusing from the center to the periphery. This structure, also observed in close and distant species such as dolphins, hippopotamus, rhinoceros, and elephants, is poorly described, nor are the LN macrophage populations and their relationship with B cell follicles. B cell maturation occurs mainly in LN B cell follicles with the help of LN macrophage populations endowed with different antigen delivery capacities. We identified three macrophage populations that we localized in the inverted LN spatial organization. This allowed us to ascribe porcine LN MΦ to their murine counterparts: subcapsular sinus MΦ, medullary cord MΦ and medullary sinus MΦ. We identified the different intra and extrafollicular stages of LN B cells maturation and explored the interaction of MΦ, drained antigen and follicular B cells. The porcine reproductive and respiratory syndrome virus (PRRSV) is a major porcine pathogen that infects tissue macrophages (MΦ). PRRSV is persistent in the secondary lymphoid tissues and induces a delay in neutralizing antibodies appearance. We observed PRRSV interaction with two LN MΦ populations, of which one interacts closely with centroblasts. We observed BCL6 up-regulation in centroblast upon PRRSV infection, leading to new hypothesis on PRRSV inhibition of B cell maturation. This seminal study of porcine LN will permit fruitful comparison with murine and human LN for a better understanding of normal and inverted LN development and functioning.

Highlights

In most species, free antigens and DC migrating from the peripheral tissues enter the lymph node (LN) through the afferent lymphatic vessels into the external capsular sinus
We first explored the inverted structure of the pig lymph nodes (LN) according to LN M populations and B cell maturation stages
The efferent M (effM) population had a subcapsular localization at the exit of the LN, whereas human and mice subcapsular sinus M (SCS M) are positioned at the entrance of the LN

Summary

Introduction

Free antigens and DC migrating from the peripheral tissues enter the lymph node (LN) through the afferent lymphatic vessels into the external capsular sinus. Upon antigen encounter in the context of the adequate antigen presenting cells, T and B lymphocytes get activated, mature and exit the LN through the medullary sinus and the efferent lymphatic vessel. The porcine afferent lymphatic vessels enter the capsule at one site and penetrate deep into the area occupied by the B follicles and the T cells. They join the trabecular sinuses and filters into the subcapsular sinus from which efferent vessels originate [5]. Naïve lymphocytes entered the LN through HEV as in other mammalian species, after having scanned the B and T cell areas, they exit directly in the blood through the same HEV [6]

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Results

Conclusion