Research ArticleINFECTIOUS DISEASE

The human thymus perivascular space is a functional niche for viral-specific plasma cells

Science Immunology  23 Dec 2016:
Vol. 1, Issue 6,
DOI: 10.1126/sciimmunol.aah4447

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Not in the thymic house

The human thymus is the seat of T cell production, and thymic infection can alter both thymopoiesis and tolerance. Circulating antibodies from bone marrow–resident plasma cells have been shown to help protect the thymus from infection; however, the contribution of thymic-resident B cells has remained unclear. Now, Nuñez et al. report that plasma cells reside in the human thymus and that these plasma cells produce antibodies reactive to common viral proteins. These cells inhabit the thymic perivascular space, located between the thymic epithelial areas and the circulation, and therefore may fortify the thymus against pathogen invasion. These cells are maintained in aging individuals, suggesting that thymic plasma cells play a key role in thymic protection throughout the human life span.

Abstract

The human thymus is susceptible to viral infections that can severely alter thymopoiesis and compromise the mechanisms of acquired tolerance to self-antigens. In humans, plasma cells (PCs) residing primarily in the bone marrow confer long-lasting protection to common viruses by secreting antigen-specific antibodies. Because the thymus also houses B cells, we examined the phenotypic complexity of these thymic resident cells and their possible protective role against viral infections. Using tissue specimens collected from patients ranging in age from 5 days to 71 years, we found that, starting during the first year of life, CD138+ PCs begin accumulating in the thymic perivascular space (PVS), where they constitutively produce immunoglobulin G (IgG) without the need for additional stimulation. These thymic PCs almost exclusively secrete IgG1 and IgG3, the two main complement-fixing effector IgG subclasses. Moreover, using antigen-specific enzyme-linked immunospot assays, we demonstrated that thymic PCs include a high frequency of cells reactive to common viral proteins. Our study reveals an unrecognized role of the PVS as a functional niche for viral-specific PCs. The PVS is located between the thymic epithelial areas and the circulation. PCs located in this compartment may therefore provide internal protection against pathogen infections and preserve the integrity and function of the organ.

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