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Arthritis Rheumatol. 2017 May;69(5):1078-1089. doi: 10.1002/art.40016.

Scleroderma Peripheral B Lymphocytes Secrete Interleukin-6 and Transforming Growth Factor β and Activate Fibroblasts.

Author information

1
INSERM U1016, Institut Cochin, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, LabEx Inflamex, Université Sorbonne Paris Cité and Université Paris Diderot, Paris, France.
2
INSERM U1016, Institut Cochin, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité and Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes Rares, Vascularites Nécrosantes et Sclérodermie Systémique, Hôpital Cochin, AP-HP, Paris, France.
3
INSERM U1016, Institut Cochin, CNRS UMR 8104 and Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
4
Université Paris XIII, UFR Santé Médecine Biologie Humaine and INSERM U978, Bobigny, France.
5
Service d'Anatomie Pathologique, Hôpital Marie Lannelongue, INSERM UMR-S 999, LabEx LERMIT, Le Plessis-Robinson, France.
6
Université Paris Descartes, Sorbonne Paris Cité and Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes Rares, Vascularites Nécrosantes et Sclérodermie Systémique, Hôpital Cochin, AP-HP, Paris, France.
7
Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes Rares, Vascularites Nécrosantes et Sclérodermie Systémique, Hôpital Cochin, AP-HP, Paris, France.
8
LabEx Inflamex, Université Sorbonne Paris Cité, Paris, and Université Paris XIII, UFR Santé Médecine Biologie Humaine and INSERM U978, Bobigny, France.
9
INSERM U1016, Institut Cochin, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris Cité, LabEx Inflamex, Université Sorbonne Paris Cité and Service de Médecine Interne, Centre de Référence Maladies Systémiques Autoimmunes Rares, Vascularites Nécrosantes et Sclérodermie Systémique, Hôpital Cochin, AP-HP, Paris, France.

Abstract

OBJECTIVE:

To study the role of B lymphocytes in systemic sclerosis (SSc).

METHODS:

Peripheral B cell subpopulations and the production of interleukin-6 (IL-6) and transforming growth factor β (TGFβ) were analyzed using flow cytometry and multiplex assay. The fibroblast proliferation rate upon incubation with supernatants from B cells isolated from SSc patients or healthy controls was assessed using XTT, bromodeoxyuridine, and Ki-67. Collagen production was assessed using a collagen assay.

RESULTS:

Ninety untreated patients (12 males) fulfilling the American College of Rheumatology/European League Against Rheumatism criteria for SSc (23 with diffuse cutaneous SSc [dcSSc] and 67 with limited cutaneous SSc [lcSSc]) and 30 healthy controls were recruited. Increased proportions of B cells expressing CD69 and CD95 were identified among the patients with SSc. B lymphocytes from dcSSc patients versus lcSSc patients and healthy controls expressed increased proportion of cells positive for CD5 (mean ± SD 24.12 ± 7.93% versus 14.09 ± 6.58% [P = 0.03] and 14.21 ± 5.34% [P = 0.01]), CD86 (39.89 ± 22.11% versus 17.72 ± 13.98% [P = 0.0007] and 11.68 ± 11.09% [P < 0.001]), IL-6 receptor (IL-6R; 33.64 ± 23.12% versus 17.91 ± 13.62% [P < 0.0001] and 12.08 ± 8.68% [P = 0.0009]), or IL-21R (32.55 ± 20.19% versus 5.76 ± 4.40% [P < 0.0001] and 5.93 ± 3.29% [P < 0.0001]). In addition, the levels of IL-6 (mean ± SD 314.3 ± 317.8 pg/ml versus 6.10 ± 2.58 pg/ml; P = 0.0007) and TGFβ (mean ± SD 1,020 ± 569 pg/ml versus 163.8 ± 98.69 pg/ml; P = 0.001) secreted by B lymphocytes from patients with SSc were increased compared to healthy controls. Fibroblast proliferation and collagen production were also significantly increased in the presence of B cell supernatant from SSc patients as compared to healthy controls.

CONCLUSION:

The numbers of activated B cells were increased in SSc patients, and the up-regulation of CD5, CD86, IL-6R, and IL-21R discriminated between patients with dcSSc and those with lcSSc. Peripheral B lymphocytes from SSc patients secreted both IL-6 and TGFβ, and they activated fibroblasts in vitro.

PMID:
27992693
DOI:
10.1002/art.40016
[Indexed for MEDLINE]
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