Publication Date
2016
Journal Title
J Leukoc Biol
Abstract
This study tested the hypothesis that B cells from salivary tissue are distinct in terms of proliferative capacity, immunoglobulin M secretion, repertoire, and autoantibody enrichment in Sjogren's syndrome. We sorted purified B cells from the spleen, cervical lymph nodes, and submandibular glands of a primary Sjogren's syndrome mouse model (Id3-/-). Enzyme-linked immunospot and proliferation assays were performed with stimulated B cells. We single-cell sorted B cells from the spleen, cervical lymph nodes, and submandibular gland tissue from Sjogren's syndrome mice and sequenced immunoglobulin M heavy-chain variable regions. Finally, autoantigen arrays were performed using immunoglobulin M derived from sera, cervical lymph nodes, spleens, and submandibular gland tissue of Id3-/- animals. Results suggest B cells from salivary tissue of Sjogren's syndrome mice are similar to those from secondary immune sites in terms of proliferative and secretory capacity. However, differences in repertoire usage, heavy chain complementarity-determining region 3 length, mutational frequency, and N region addition were observed among B cells derived from submandibular gland, cervical lymph node, and spleen tissue. Moreover, autoantigen array data show immunoglobulin M from salivary B cells have enriched specificity for Ro (Sjogren's syndrome A) and La (Sjogren's syndrome B). All together, these data suggest salivary B cells have unique repertoire characteristics that likely influence autoantigen binding and contribute to Sjogren's syndrome disease in a tissue-specific manner.
Volume Number
99
Issue Number
2
Pages
321-31
Document Type
Article
EPub Date
2015/09/19
Status
Faculty, Northwell Researcher
Facility
School of Medicine; Northwell Health
Primary Department
Molecular Medicine
Additional Departments
General Internal Medicine
PMID
DOI
10.1189/jlb.2A0715-297R