Article
A non-naïve and autoimmune prone IgD+ B cell pool is selectively supported by fibroblast like synoviocytes (FLS)
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Authors
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Dennis Bleck
- Hiller Forschungszentrum Rheumatologie, Universitätsklinikum Düsseldorf, Rheumatologie, Düsseldorf
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Matthias Schneider
- Universitätsklinikum Düsseldorf, Poliklinik und Funktionsbereich für Rheumatologie, Düsseldorf
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Georg Pongratz
- Universitätsklinikum Düsseldorf Heinrich-Heine-Universität, Poliklinik und Funktionsbereich für Rheumatologie & Hiller Forchungszentrum für Rheumatologie, Düsseldorf
| Published: | September 9, 2020 |
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Outline
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Introduction: IgD+ B cells show increased autoimmune potential compared to other subpopulations and serum IgD levels are increased in autoimmune disease [1], [2]. We investigated B cell-FLS co-cultures because FLS might be an essential factor in promoting the IgD+ B cell pool.
Methods: Peripheral total IgD+ B cells (DBC) and naïve B cells (NBC) were isolated from healthy donors by MACS and co-cultured with or w/o SFs in medium only or in the presence of IL-4. B cell subpopulations and survival were determined by FACS. Secreted IgG and IgD were measured by ELISA. Activation induced deaminase (AID) expression was demonstrated by in-situ PCR.
Results: After 3 days in culture, plasma cells (CD19-CD138+) were increased in NBC co-cultures as compared to DBC co-cultures (NBC: 0.045% of total B cells +/-0.03%; DBC: 0.01% of total B cells +/-0.01 %; p=0.03; IL-4: NBC: 0.14% of total B cells +/-0.08%; DBC: 0.015% of total B cells +/-0.015 %; p=0,03 ). Of these plasma cells, the IgG+ (switched) population was increased in NBC co-cultures as compared to DBC co-cultures in the presence of IL-4 (NBC: 48.9% of CD19-CD138+ B cells +/-40.42%; DBC: 0 % of CD19-CD138+ B cells +/- 0%; p=0.06). The memory B cell pool (CD19+CD27+) was expanded in DBC co-cultures compared to NBC co-cultures (DBC: 2.97% of total B cells +/-0.24%; NBC: 0.74% of total B cells +/-0.72%; p<0.001; IL-4: DBC: 6.24% of total B cells +/-0.21%; NBC: 0.8% of total B cells +/-0.38%; p < 0.001). Of these memory B cells, the IgD+ (non-switched) population was increased in the NBC co-cultures compared to the DBC co-cultures (naive: 82.7% of CD19+CD27+ B cells +/-11.5%; IgD+: 50.9% of CD19+CD27+ B cells +/-7.6%; p=0.001). IgG concentration in NBC co-culture supernatant was increased compared to DBC co-cultures (NBC: 153.5 ng/mL +/-8.8 ng/mL; DBC: 22.2 ng/mL +/-0.6 ng/mL; p = 0.02), while IgD concentration showed the opposite (NBC: non-detectable; DBC: 55 ng/mL +/-0.3 ng/mL; p<0.001). In-situ PCR proofed expression of AID in NBC co-culture.
Conclusion: It is not known why the autoimmune-prone IgD+ B cell pool is expanded in RA patients; in this regard, our data provide evidence, that FLS might be one pivotal factor for explaining this observation.
Disclosures: No conflicts of interest
References
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- 2.
- Pope RM, Keightley R, McDuffy S. Circulating autoantibodies to IgD in rheumatic diseases. J Immunol. 1982 Apr;128(4): 1860-3.
