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© The Rockefeller University Press, 0022-1007/1997/6/1909/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 11, June 2, 1997 1909-1918

Article

Human Dendritic Cells Skew Isotype Switching of CD40-activated Naive B Cells towards IgA1 and IgA2

Jérôme Fayette, Bertrand Dubois, Stéphane Vandenabeele, Jean-Michel Bridon, Béatrice Vanbervliet, Isabelle Durand, Jacques Banchereau, Christophe Caux, and Francine Brière

From Schering-Plough, Laboratory for Immunological Research, Dardilly, France

Within T cell–rich areas of secondary lymphoid organs, interdigitating dendritic cells recruit antigen-specific T cells that then induce B cells to secrete Igs. This study investigates the possible role(s) of dendritic cells in the regulation of human B cell responses. In the absence of exogenous cytokines, in vitro generated dendritic cells (referred to as Dendritic Langerhans cells, D-Lc) induced surface IgA expression on ~10% of CD40-activated naive sIgD+ B cells. In the presence of IL-10 and TGF-β, a combination of cytokines previously identified for its capacity to induce IgA switch, D-Lc strongly potentiated the induction of sIgA on CD40-activated naive B cells from 5% to 40–50%. D-Lc alone did not induce the secretion of IgA by CD40-activated naive B cells, which required further addition of IL-10. Furthermore, D-Lc skewed towards the IgA isotype at the expense of IgG, the Ig production of CD40-activated naive B cells cultured in the presence of IL-10 and TGF-β. Importantly, under these culture conditions, both IgA1 and IgA2 were detected. In the presence of IL-10, secretion of IgA2 by CD40-activated naive B cells could be detected only in response to D-Lc and was further enhanced by TGF-β. Collectively, these results suggest that in addition to activating T cells in the extrafollicular areas of secondary lymphoid organs, human D-Lc also directly modulate T cell–dependent B cell growth and differentiation, by inducing the IgA isotype switch.

Address correspondence to Dr. Francine Brière, Schering-Plough Laboratory for Immunological Research, 27 chemin des Peupliers, BP11, 69571, Dardilly, France.

1 Abbreviations used in this paper: CD40L, CD40 ligand; CD40L-L cells, CD40L-transfected L cells; DC, dendritic cells; D-Lc, dendritic Langerhans cells; sIg, surface immunoglobulins; IL-10, interleukin 10; TGF-β, transforming growth factor β.


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