Impacts of CD40- and CD86-Silenced Antigen-Specific B Cells on the Control of Allergies.

Abstract

Background We previously reported that CD40-silenced B cells inhibited allergic responses and symptoms. However, more potent therapies are needed. To our knowledge, the effects of CD86-silenced B cells and synergic effects of gene silencing in B cells by 2 small interfering RNAs (siRNAs) on allergic disease control have not been reported. Objective To investigate the effects of CD86-silenced B cells and synergic effects of gene silencing in B cells on allergic responses and symptoms. Methods Mice were treated with CD40- and/or CD86-silenced B cells transfected with siRNAs and pulsed with ovalbumin (OVA). And the effects of these B cells were estimated. Results CD86-silenced OVA-pulsed B cells significantly inhibited OVA-induced allergies. Treatment with CD40-/CD86-silenced OVA-pulsed B cells led to a significantly fewer sneezes and nasal rubbing movements, as well as lower OVA-specific immunoglobulin E (IgE) levels, than that with CD40-silenced or CD86-silenced OVA-pulsed B cells alone. These inhibitory effects were observed prior to sensitization as well as after the establishment of allergic rhinitis. CD40-/CD86-silenced OVA-pulsed B cells did not inhibit keyhole limpet hemocyanin-induced allergies. CD40-/CD86-silenced OVA-pulsed B cells also significantly inhibited allergic symptoms and OVA-specific IgE level in sera compared with CD40-/CD86-silenced OVA-pulsed dendritic cells (DCs). In addition, CD19+CD40− B cells significantly increased in the nasal tissue after intravenous administration of these cells. Furthermore, CD40-/CD86-silenced B cells inhibited allergic symptoms caused by Cry j 1, a major aeroallergen of Japanese cedar pollen, and Cry j 1-specific IgE in sera. Conclusion This study showed, for the first time, that siRNA-induced CD86-silenced B cells significantly inhibited allergic responses and symptoms antigen-specifically, and that siRNA-induced CD40-/CD86-silenced antigen-specific B cells are a more useful antigen-specific therapy than CD40- or CD86-silenced B cells alone for the control of allergies. Furthermore, it was shown that CD40-/CD86-silenced B cells have stronger inhibition of IgE production and allergic symptoms than CD40-/CD86-silenced DCs.