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

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.