Autoantigen-specific B cells and plasma cells are prominent in areas of fatty infiltration in salivary glands of patients with primary Sjögren's syndrome

Abstract

Salivary and lacrimal gland involvement is a characteristic feature of primary Sjögren's syndrome (pSS), where tissue destruction is mediated by mononuclear cell infiltration, resulting in lacrimal and salivary gland impairment. We have previously shown distinct prevalence of adipose tissue replacement in the minor salivary gland tissue from pSS patients. The salivary gland microenvironment was further examined through microarray analysis, identifying signalling pathways that promoted adipose tissue development, inflammation, and lymphoma. As B cells may also contribute to disease progression, we now aimed to study the B cell pattern with regard to adipocyte development in pSS. Double immunohistochemical staining of paraffin-embedded salivary gland tissue from 22 pSS patients and 11 non-SS tissue controls was employed, using the characteristic pSS autoantigens Ro52 or Ro60, alongside CD27. Additional CD138/CD20 double staining was also performed to identify the plasma- and general B- cell pattern. Our results demonstrated CD27-positive Ro52 and Ro60 specific cells observed within and in close proximity to the adipose tissue. CD138-positive plasma cells were also seen in areas of adipose tissue replacement, while the CD20⁺ cells were located within focal infiltrates, forming distinct B cell zones. The quantification of CD138⁺ and CD20⁺ cells revealed elevated numbers of CD138⁺ cells in areas of fatty infiltration, and also interstitially, in the salivary glands of pSS patients when compared to non-SS controls. A significant increase (p < .01) in CD138⁺ cells close to areas of fatty infiltration, and interstitially, with increasing fatty infiltration and focus score was further observed in pSS patients. A correlation between the number of CD20⁺ B cell zones/mm² of salivary gland tissue and focus score values was also witnessed in the patients (r² = 0.6047, p < .001). In conclusion, autoantigen-specific B cells and plasma cells appear prominent in areas of fatty infiltration in salivary glands of pSS patients, where an increase in CD138⁺ plasma cells and CD20⁺ B cells, in relation to both fatty and focal infiltration, suggests their active involvement in promoting inflammation. Further studies are needed to assess whether these adipocytes are also a result of tissue repair.

Keywords: B cells; Fatty infiltration; Sjögren’s syndrome; adipocytes; autoantigens; autoimmunity; plasma cells; salivary glands.