Introduction Tertiary lymphoid structures (TLS) characterised by germinal centre formation and B cell proliferation represent the histological hallmark of primary Sjögren’s syndrome (pSS). However, the events preceding the formation of such ectopic structures and factors driving their persistence are unknown. Overexpression of BAFF, also known as B cell lymphocyte stimulator (BLyS), in pSS patients has been linked with the presence of autoreactive B cells and autoantibody production.¹ Furthermore, in pSS salivary glands BAFF is associated with the expansion of specific B cell subsets, and with B cell repopulation post rituximab treatment.²

Objectives In this work we aimed to dissect the dynamics of B cell subsets within tertiary lymphoid structures following BAFF-targeted treatment in both inducible and chronic animal models that mimic the histological features of pSS.

Methods Submandibular salivary glands of C57BL/6 mice were intra-ductally cannulated with luciferase-encoding replication-deficient adenovirus to induce TLS formation as previously described.³ Prior to salivary gland cannulation, mice were treated with two doses (i.p.) of either anti-BLyS mAb or isotype control. Salivary glands were dissected at day 15 post-cannulation and TLS formation in both groups was assessed. NOD.B10.H2b mice were similarly treated with anti-BLyS mAb at 26 weeks old and salivary gland infiltrates assessed 21 days later.

Results Histological analysis of salivary glands from anti-BLyS treated C57BL/6 animals unveiled severely compromised TLS formation. Post anti-BLyS treatment, salivary glands were infiltrated by T cell clusters but only few, and scattered, B cells were present, contrasting with fully developed and organised TLS in the salivary glands of mice treated with isotype control. Significantly lower numbers of B cells, particularly from the B2 subset, as well as plasmablasts, infiltrated salivary glands of anti-BLyS treated mice. However, treatment with anti-BLyS did not affect numbers of infiltrating T cells (both CD4 and CD8), proliferative T cells, or plasma cells in inflamed salivary glands. In a chronic setting, salivary glands from NOD.B10.H2b mice were also infiltrated by significantly lower numbers of B2 B cells following anti-BLyS treatment.

Conclusions Our data highlights BAFF as a key player in ectopic lymphoneogenesis during inflammation as well as a subset-specific role for BAFF in B cell maturation. Furthermore, these results support future studies of BAFF-targeted therapeutics in pSS.

References

1. . Pers, et al. Ann N Y Acad Sci2005.

2. . Pers, et al. Arthritis Rheum2007.

3. . Bombardieri, Barone, et al. JI2012.

Acknowledgements This research is funded by GSK.

Disclosure of interest J. Campos: None declared, T. Slocombe Employee of: GSK, S. Nayar: None declared, V. Iannizzotto: None declared, D. Gardner: None declared, C. Buckley: None declared, A. Haynes Employee of: GSK, R. Henderson Employee of: GSK, F. Barone: None declared