Human Dendritic/Langerhans Cells Control Growth and Differentiation of CD40 Activated B Cells

Abstract

During an immune response, dendritic cells (DC) capture the antigen at site of injury, and migrate through the afferent lymph stream to the lymph-nodes where they efficiently activate naive T cells. This T cell activation is followed by B cell recruitment, which occurs in the extrafollicular area, where DC home¹. Accordingly, we wondered herein whether DC might directly interact with B cells, using DC generated in vitro from CD34⁺ progenitors, called Dendritic-Langerhans cells^2,3 (D-Lc). As both DCs⁴ and B cells⁵ express functional CD40, we used CD40-ligand transfected L cells⁶ as surrogate activated T cells, to study the effect of DCs on B cell activation. We show that D-Lc enhanced the proliferation of CD40-activated naive B cells and Ig commited B lymphocytes (3–8 fold). In addition, D-Lc induced a 10 to 100 fold enhancement of IgG and IgA secretions by Ig committed B cells (essentially memory B cells). Most notably, in the presence of IL-2, D-Lc stimulated CD40-activated naive B cells to produce high amounts of IgM. Using transwells, we showed that the effect on B cell proliferation is soluble and independent of CD40 triggering on D-Lc. In contrast, the IgM production is partly dependent of soluble molecule(s) secreted after CD40 engagement on D-Lc. The use of anti-cytokine blocking antibodies indicate that D-Lc derived IL-12 is absolutely required (although not sufficient) for the differentiation of naive B cells into 1gM secreting cells in presence of IL-2.