Tissue-Specific Expansion of Age-Associated B Cells via IFN-γ and IL-21 Within Salivary Glands in Sjögren Disease.

T-bet+ CD20+ ABCs were detected infiltrating labial salivary glands in SjD patients, particularly in individuals in their 40s–60s, but were rare in non-SjD sicca controls.

• Study examined labial salivary glands (LSGs) from 44 SjD patients and 11 non-SjD sicca controls.
• ABCs were identified as T-bet+ CD20+ cells infiltrating the glands.
• ABC infiltration was especially prominent in SjD patients in their 40s–60s.
• ABCs were rare in non-SjD sicca controls, indicating disease-specific accumulation.

In the SjD mouse model, ABCs began locally accumulating in salivary glands from the mature-adult stage, earlier than in age-matched controls, while remaining low in cervical lymph nodes.

• ABCs were defined as CD11b+ CD95+ CD19+ cells in the mouse model.
• Local accumulation in salivary glands began at the mature-adult stage in SjD model mice.
• Accumulation occurred earlier than in age-matched non-SjD controls.
• ABC levels remained low in cervical lymph nodes (cLNs), indicating tissue-specific expansion rather than systemic increase.

The combination of IL-21 and IFN-γ upregulated T-bet expression on B cells in SjD model mice.

• The study focused on IL-21 and IFN-γ as drivers of ABC differentiation.
• T-bet upregulation on B cells was observed when both cytokines were present together.
• This finding was demonstrated using the SjD mouse model system.

CD4+ T cells, especially follicular helper T (Tfh)-like cells, were identified as a major source of IL-21 in the salivary glands of mature-adult SjD mice.

• Both in situ hybridization (ISH) and flow cytometric analysis were used to identify IL-21-producing cells.
• Tfh-like cells were identified as the predominant IL-21-producing population within the salivary glands.
• This IL-21 source was localized to salivary glands of mature-adult SjD model mice.
• The finding points to local T cell–B cell interactions as a mechanism driving ABC expansion.

ABCs themselves showed elevated IFN-γ expression compared to other immune cells in salivary glands, indicating an autocrine mechanism promoting their expansion.

• IFN-γ expression by ABCs was higher than in other immune cell populations examined.
• This autocrine IFN-γ activity was identified as a mechanism that may sustain or amplify ABC expansion.
• The finding was established through flow cytometric analysis in the SjD mouse model.

Advancing age is recognized as an important risk factor for Sjögren disease development, but the mechanisms linking age and disease progression have remained poorly understood.

• SjD is described as an autoimmune disorder that predominantly affects the exocrine glands.
• ABCs are a subset of B cells that increase with age and have been implicated in autoimmune responses.
• Prior to this study, the role of ABCs in SjD pathogenesis had not been fully clarified.