Article Text

PDF

Toll-like receptor 9 (TLR9) controls B cell differentiation in salivary glands of patients with sjögren’s syndrome
  1. C Jamin,
  2. T Guerrier,
  3. L Le Pottier,
  4. A Saraux,
  5. P Youinou,
  6. J Pers
  1. EA 2216 « Immunologie et Pathologie » and IFR 148 ScInBioS, Université de Brest Université Européenne de Bretagne, Brest, France

Statistics from Altmetric.com

Background

B cell clusters represent genuine germinal centres in the salivary glands of patients with Sjögren’s syndrome, but the majority display transitional and marginal zone (MZ)-like B cell characteristics. The authors questioned whether TLR9 stimulation, which occurs during inflammatory reactions, could influence such an aberrant B cell differentiation.

Methods

Following laser microdissection, TLR expression was measured in B cell aggregates using quantitative RT-PCR. As controls, transitional and mature B cells from cord blood and tonsils were FACS sorted and stimulated with CpG-ODN. CFSE enabled evaluation of their proliferation, and they were also analysed by flow cytometry to determine their activation status. Differentiation into Ig-secreting cells was demonstrated by ELISA.

Results

Transitional B cell aggregates of salivary glands expressed a high level of TLRs whereas real germinal centres lacked TLR expression. In vitro, TLR9 stimulation induced proliferation of transitional B cells, activation and maturation as MZ B cells (Notch2high, CD21high, IgMhigh, IgDlow, CD23low, CD27). Mature B cells also proliferated but differentiated toward a follicular pathway (Notch2low, IgMlow, IgDlow, CD23low, CD27). Production of Ig was observed in both B cell supernatants.

Conclusion

High TLR level in transitional salivary gland B cell aggregates indicates how highly sensitive to inflammatory stimuli they are. Immature B cells can differentiate into Ig-secreting cells following TLR9 stimulation through a MZ-like maturation pathway without entering the germinal centres. In contrast, mature B cells differentiate towards a classical follicular pathway. Whether one or both differentiation pathways generate autoreactive B cells in salivary glands remains to be established in patients with Sjögren’s syndrome.

View Abstract

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.