# Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation

**Authors:** Lilian Soto, Ashley Ferrier, Octavio Aravena, Elianet Fonseca, Jorge Berendsen, Andrea Biere, Daniel Bueno, Verónica Ramos, Juan Carlos Aguillón, Diego Catalán

PMC · DOI: 10.3389/fimmu.2015.00496 · Frontiers in Immunology · 2015-09-29

## TL;DR

This study finds that systemic sclerosis patients have altered B-cell regulation molecules, which may contribute to autoimmunity.

## Contribution

The study identifies specific B-cell receptor expression changes in systemic sclerosis patients compared to healthy controls.

## Key findings

- Systemic sclerosis patients have increased transitional and naive B cells relative to memory B cells.
- B cells from patients show higher CD86 and FcγRIIB expression and reduced IL-10 production.
- CD19 and CD35 levels correlate with autoantibody profiles in systemic sclerosis patients.

## Abstract

The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10+ B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis.

## Linked entities

- **Genes:** CD86 (CD86 molecule) [NCBI Gene 942], H2 (histocompatibility-2, MHC) [NCBI Gene 111364], CD19 (CD19 molecule) [NCBI Gene 930], CR2 (complement C3d receptor 2) [NCBI Gene 1380], CD40 (CD40 molecule) [NCBI Gene 958], CD22 (CD22 molecule) [NCBI Gene 933], SIGLEC10 (sialic acid binding Ig like lectin 10) [NCBI Gene 89790], CR1 (complement C3b/C4b receptor 1 (Knops blood group)) [NCBI Gene 1378], IL10 (interleukin 10) [NCBI Gene 3586], IL6 (interleukin 6) [NCBI Gene 3569]
- **Diseases:** systemic sclerosis (MONDO:0005100)

## Full-text entities

- **Genes:** Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, CR1 (complement C3b/C4b receptor 1 (Knops blood group)) [NCBI Gene 1378] {aka C3BR, C4BR, CD35, KN}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, CD1D (CD1d molecule) [NCBI Gene 912] {aka R3, R3G1}, CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, Cr2 (complement receptor 2) [NCBI Gene 12902] {aka C3DR, CD21, CD35, Cr-1, Cr-2, Cr1}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Ifitm3 (interferon induced transmembrane protein 3) [NCBI Gene 66141] {aka 1110004C05Rik, Cd225, Cdw217, DSPA2b, Fgls, IP15}, CD24 (CD24 molecule) [NCBI Gene 100133941] {aka CD24A}, CR2 (complement C3d receptor 2) [NCBI Gene 1380] {aka C3DR, CD21, CR, CVID7, SLEB9}, Cd19 (CD19 antigen) [NCBI Gene 12478], CD40LG (CD40 ligand) [NCBI Gene 959] {aka CD154, CD40L, HIGM1, IGM, IMD3, T-BAM}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CD81 (CD81 molecule) [NCBI Gene 975] {aka CVID6, S5.7, TAPA1, TSPAN28}, TSKU (tsukushi, small leucine rich proteoglycan) [NCBI Gene 25987] {aka E2IG4, LRRC54, TSK}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, SIGLEC10 (sialic acid binding Ig like lectin 10) [NCBI Gene 89790] {aka PRO940, SIGLEC-10, SLG2}, CD22 (CD22 molecule) [NCBI Gene 933] {aka SIGLEC-2, SIGLEC2}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, BCR (BCR activator of RhoGEF and GTPase) [NCBI Gene 613] {aka ALL, BCR1, CML, D22S11, D22S662, PHL}, Fcgr2b (Fc receptor, IgG, low affinity IIb) [NCBI Gene 14130] {aka CD32, F630109E10Rik, Fc[g]RII, FcgRII, Fcgr2, Fcgr2a}, FCGR2B (Fc gamma receptor IIb) [NCBI Gene 2213] {aka CD32, CD32B, FCG2, FCGR2, IGFR2}, CD27 (CD27 molecule) [NCBI Gene 939] {aka S152, S152. LPFS2, T14, TNFRSF7, Tp55}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, Cd22 (CD22 antigen) [NCBI Gene 12483] {aka A530093D23, Lyb-8, Lyb8}
- **Diseases:** autoimmune (MESH:D001327), systemic autoimmune disease (MESH:D020274), vasculopathy (MESH:D000090122), SSc (MESH:D012595), Peripheral vascular 16 (MESH:D016491), diffuse cutaneous (MESH:D045743), Fibrosis (MESH:D005355), RA (MESH:D001172), interstitial lung disease (MESH:D017563), primary Sjogren's syndrome (MESH:D012859), arthritis (MESH:D001168), cutaneous (MESH:D018366), Gastrointestinal tract (MESH:D005770), Skin (MESH:D012871), SLE (MESH:D008180), Heart (MESH:D006331), pulmonary arterial hypertension (MESH:D000081029)
- **Species:** Stenocactus sp. SC (species) [taxon 867526], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4586944/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC4586944/full.md

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Source: https://tomesphere.com/paper/PMC4586944