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Arthritis Rheumatol. 2018 Jul 29. doi: 10.1002/art.40682. [Epub ahead of print]

SLAMF1 engagement inhibits T cell-B cell interaction and diminishes IL-6 production and plasmablast differentiation in systemic lupus erythematosus.

Author information

1
Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
2
Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, CH, 1011, Lausanne, Switzerland.

Abstract

OBJECTIVE:

SLAMF1 homophilic interactions promote immunoglobulin production and T cell-B cell (T-B) cross-talk. SLAMF1 is overexpressed on T and B cells in patients with SLE. We conducted studies to determine the role of SLAMF1 monoclonal antibody in modulating T-B cell interaction and B cell activation.

MATERIALS:

Anti-IgM pre-stimulated naïve or total B cells from healthy donors or patients with SLE were co-cultured with autologous T cells under CD3/CD28 stimulation in the presence or absence of SLAMF1 monoclonal antibody. Naïve B cells were stimulated with anti-IgM and CD40L in the presence of SLAMF1 antibody. Cytokine production by CD4+ T cells and B cells was examined by flow cytometry and/or qPCR. Plasmablast formation and T-B conjugates were assessed by flow cytometry. IgG and ANA production was determined by ELISA.

RESULTS:

SLAMF1 ligation in a human peripheral blood T-B cell culture system reduces conjugate formation, IL-6 production by B cells, IL-21 and IL-17A by T cells, Ig and autoantibody production in both healthy controls and patients with SLE. Whereas the SLAMF1 monoclonal antibody affects directly the function of isolated peripheral B cells by decreasing IL-6 and Ig production in vitro, it does not affect stimulation and cytokine production by isolated T cells stimulated in vitro.

CONCLUSIONS:

SLAMF1 antibody inhibits T-B cell interaction and suppresses B cell cytokine production and differentiation and therefore it represents a therapeutic tool in the treatment of patients with SLE. This article is protected by copyright. All rights reserved.

KEYWORDS:

SLE ; B cells; IL-6; SLAMF1; autoimmunity

PMID:
30058241
DOI:
10.1002/art.40682

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