Utilization of a Lentiviral System for the Generation of B Cells with Regulatory Properties

Abstract

B cells are classically considered for their unique capacity to produce antibodies. Besides this, B cells can also present antigen, costimulate T cells, and secrete cytokines. Recent studies have demonstrated that activated B cells could regulate immunity by the secretion of anti-inflammatory cytokines. Because of their capacity to inhibit immune responses, B cells became of interest as a potential vehicle for the treatment of autoimmune disorders via cell-based therapy. Different approaches have been developed to empower B cells with regulatory properties. An attractive strategy involves their genetic engineering to enforce their expression of suppressive genes. This can be achieved using retroviral vectors. However, most retroviral vectors require prior activation of the B cells for transduction, and the administration of activated B cells may lead to unpredictable outcomes in recipients, including to an enhancement of immune responses. In contrast, resting B cells are poorly immunogenic and therefore safer for the suppression of undesired immune responses in adoptive cell therapy. In this chapter, we describe an approach to generate genetically modified resting B cells with lentiviral vectors using a protocol that is rapid, simple, and neither requires nor induces activation of B cells.

Collagen epitope expression on B cells is sufficient to confer tolerance to collagen-induced arthritis

“…Antigen presentation by B cells prevents cognate activation of naive, but not memory, T cells [ 32 ] and induces tolerance to soluble antigen [ 33 ]. B cells can also induce and maintain tolerance by production of anti-inflammatory cytokines such as IL-10, and B cells genetically or otherwise manipulated to produce IL-10 have immunoregulatory properties in autoimmune diseases [ 6 , 7 , 21 , 34 ]. Gene therapy reintroducing Wiskott–Aldrich protein in B cells prevented development of autoreactive B-cell clones in Wiskott–Aldrich syndrome patients [ 35 ], highlighting the importance of B cells for tolerance.…”

Tolerance in Kidney Transplantation: What Is on the B Side?

“…Since most of the induction systems used at this moment promote activation of B cells, Fillatreau and colleagues propose a method to induce IL-10 expression on resting B cells to generate tolerogenic B cells which are poor immunogenic and present a lower potential risk of switching into effector B cell [72]. Another matter of concern is the antigen specificity of Breg.…”