Salivary glands act as mucosal inductive sites via the formation of ectopic germinal centers after site‐restricted MCMV infection

• Published in: The FASEB journal 2011-05, Vol.25 (5), p.1680-1696
• Main Authors: Grewal, Jasvir S., Pilgrim, Mark J., Grewal, Suman, Kasman, Laura, Werner, Phillip, Bruorton, Mary E., London, Steven D., London, Lucille
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Viral - immunology; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Germinal Center - immunology; Immunohistochemistry; Lymphocytes - immunology; Mice; Mice, Inbred BALB C; mucosal immunity; Muromegalovirus - immunology; Research Communications; Reverse Transcriptase Polymerase Chain Reaction; Salivary Glands - immunology; viral immunity
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.10-174656

ABSTRACT We investigated the hypothesis that salivary gland inoculation stimulates formation of ectopic germinal centers (GCs), transforming the gland into a mucosal inductive site. Intraglandular infection of mice with murine cytomegalovirus (MCMV; control: UV‐inactivated MCMV) induces salivary gland ectopic follicles comprising cognate interactions between CD4+ and B220+ lymphocytes, IgM+ and isotype‐switched IgG+ and IgA+ B cells, antigen presenting cells, and follicular dendritic cells. B cells coexpressed the GC markers GCT (57%) and GL7 (52%), and bound the lectin peanut agglutinin. Lymphoid follicles were characterized by a 2‐ to 3‐fold increase in mRNA for CXCL13 (lymphoid neogenesis), syndecan‐1 (plasma cells), Blimp‐1 (plasma cell development/differentiation), and a 2‐ to 6‐fold increase for activation‐induced cytidine deaminase, PAX5, and the nonexcised rearranged DNA of an IgA class‐switch event, supporting somatic hypermutation and class‐switch recombination within the salivary follicles. Intraglandular inoculation also provided protection against a systemic MCMV challenge, as evidenced by decreased viral titers (105 plaque‐forming units to undetectable), and restoration of normal salivary flow rates from a 6‐fold decrease. Therefore, these features suggest that the salivary gland participates in oral mucosal immunity via generation of ectopic GCs, which function as ectopic muco‐sal inductive sites.—Grewal, J. S., Pilgrim, M. J., Grewal, S., Kasman, L., Werner, P., Bruorton, M. E., London, S. D., London, L. Salivary glands act as mucosal inductive sites via the formation of ectopic germinal centers after site‐restricted MCMV infection. FASEB J. 25, 1680–1696 (2011). www.fasebj.org