Early Covert Appearance of Marginal Zone B Cells in Salivary Glands of Sjögren′s Syndrome-Susceptible Mice: Initiators of Subsequent Overt Clinical Disease
Open Access
- 15 February 2021
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (4), 1919
- https://doi.org/10.3390/ijms22041919
Abstract
The C57BL/6.NOD-Aec1Aec2 mouse model has been extensively studied to define the underlying cellular and molecular bioprocesses critical in the onset of primary Sjögren’s Syndrome (pSS), a human systemic autoimmune disease characterized clinically as the loss of lacrimal and salivary gland functions leading to dry eye and dry mouth pathologies. This mouse model, together with several gene knockout mouse models of SS, has indicated that B lymphocytes, especially marginal zone B (MZB) cells, are necessary for development and onset of clinical manifestations despite the fact that destruction of the lacrimal and salivary gland cells involves a classical T cell-mediated autoimmune response. Because migrations and functions of MZB cells are difficult to study in vivo, we have carried out ex vivo investigations that use temporal global RNA transcriptomic analyses to profile autoimmunity as it develops within the salivary glands of C57BL/6.NOD-Aec1Aec2 mice. Temporal profiles indicate the appearance of Notch2-positive cells within the salivary glands of these SS-susceptible mice concomitant with the early-phase appearance of lymphocytic foci (LF). Data presented here identify cellular bioprocesses occurring during early immune cell migrations into the salivary glands and suggest MZB cells are recruited to the exocrine glands by the upregulated Cxcl13 chemokine where they recognize complement (C’)-decorated antigens via their sphingosine-1-phosphate (S1P) and B cell (BC) receptors. Based on known MZB cell behavior and mobility, we propose that MZB cells activated in the salivary glands migrate to splenic follicular zones to present antigens to follicular macrophages and dendritic cells that, in turn, promote a subsequent systemic cell-mediated and autoantibody-mediated autoimmune T cell response that targets exocrine gland cells and functions. Overall, this study uses the power of transcriptomic analyses to provide greater insight into several molecular events defining cellular bioprocesses underlying SS that can be modelled and more thoroughly studied at the cellular level.This publication has 55 references indexed in Scilit:
- Different Lymphoproliferative Disorders in Different Salivary Glands of Primary Sjögren SyndromeThe Journal of Craniofacial Surgery, 2013
- Marginal zone B cells: virtues of innate-like antibody-producing lymphocytesNature Reviews Immunology, 2013
- The Interferon-Signature of Sjögren’s Syndrome: How Unique Biomarkers Can Identify Underlying Inflammatory and Immunopathological Mechanisms of Specific DiseasesFrontiers in Immunology, 2013
- Gene Expression Profiling of Early-Phase Sjögren's Syndrome in C57BL/6.NOD-Aec1Aec2Mice Identifies Focal Adhesion Maturation Associated with Infiltrating LeukocytesInvestigative Ophthalmology & Visual Science, 2011
- Sjögren's syndrome: studying the disease in miceArthritis Research & Therapy, 2011
- Differential gene expressions in the lacrimal gland during development and onset of keratoconjunctivitis sicca in Sjögren's syndrome (SJS)-like disease of the C57BL/6.NOD-Aec1Aec2 mouseExperimental Eye Research, 2009
- Differential gene expression in the salivary gland during development and onset of xerostomia in Sjögren's syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouseArthritis Research & Therapy, 2009
- Follicular shuttling of marginal zone B cells facilitates antigen transportNature Immunology, 2007
- Sjögren's Syndrome‐Like Disease of C57BL/6.NOD‐Aec1 Aec2 Mice: Gender Differences in Keratoconjunctivitis Sicca Defined by a Cross‐Over in the Chromosome 3 Aec1 LocusScandinavian Journal of Immunology, 2006
- Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zoneNature Immunology, 2004