Passive transfer of antibodies to the linear epitope 60 kD R o 273–289 induces features of S jögren's syndrome in naive mice

Summary S jögren's syndrome ( SS ) is an autoimmune inflammatory disease that primarily affects the lacrimal and salivary glands causing dry eyes and mouth. Antibodies to R o60 are observed frequently in patients with SS ; however, the role of these antibodies in SS initiation and progression remains unclear. The sequence R o60 273–289 ( R o274) is a known B cell epitope of R o60 and antibodies to this epitope have been observed in a subset of SS patients and in animals immunized with R o60 protein. Animals immunized with R o274 linear peptide develop a S jögren's‐like illness. We hypothesized that passive transfer of anti‐ R o274‐specific immunoglobulin ( Ig)G would induce a S jögren's‐like phenotype. To evaluate this hypothesis, we adoptively transferred affinity‐purified R o274 antibodies into naive BALB /c animals, then evaluated salivary gland histology, function and IgG localization 4 days post‐transfer. At this time‐point, there was no demonstrable mononuclear cell infiltration and salivary glands were histologically normal, but we observed a functional deficit in stimulated salivary flow of animals receiving R o274 antibodies compared to animals receiving control IgG . Cellular fractionation and enzyme‐linked immunosorbent assay revealed R o274‐specific antibodies in the nucleus and cytoplasmic fractions of isolated parotid salivary gland cells that was confirmed by immunohistochemistry. These data support the hypothesis that antibodies to R o274 deposit in salivary glands can enter intact salivary gland cells and are involved in the dysregulation of salivary flow in SS .