Choosing a Dendritic Cell Profession

Abstract

Circulating monocytes can differentiate into two types of professional antigen-presenting cells: macrophages or dendritic cells (DCs). However, the factors that determine which path they follow and that govern further differentiation remain incompletely understood. Bayry et al. found that DCs derived from monocytes (mo-DCs) of people with X-linked agammaglobulinemia (XLA), who have reduced numbers of circulating B cells and thus reduced amounts of circulating immunoglobulin, showed reduced expression of DC differentiation markers compared with mo-DCs from healthy donors. Stimulation with CD40 ligand or a monoclonal antibody against CD40 promoted XLA mo-DC maturation, as did exposure to physiological levels of immunoglobulin. Moreover, CD40-reactive natural antibodies (NAbs, which are produced without stimulation by foreign antigen and are often autoreactive) isolated from immunoglobulin promoted maturation of mo-DCs from both healthy donors and individuals with XLA. However, XLA mo-DCs differentiated with CD40-reactive NAbs secreted IL-10 (which limits inflammatory responses) and showed increased immunoreactivity for cAMP response element-binding protein 1 (CREB-1), whereas XLA mo-DCs stimulated with CD40 ligand secreted interleukin-12 (IL-12, which promotes inflammatory responses) and had increased immunoreactivity for NF-κB p65, NF-κB p50, and c-Rel. Thus, the authors propose that NAbs found circulating in immunoglobulin play a role in promoting the maturation of "bystander" mo-DCs, without directly promoting their ability to stimulate an immune response. J. Bayry, S. Lacroix-Desmazes, V. Donkova-Petrini, C. Carboneil, N. Misra, Y. Lepelletier, S. Delignat, S. Varambally, E. Oksenhendler, Y. Lévy, M. Debré, M. Kazatchkine, O. Hermine, S. V. Kaveri, Natural antibodies sustain differentiation and maturation of human dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 101 , 14210-14215 (2004). [Abstract] [Full Text]