Human dendritic cells skew isotype switching of CD40-activated naive B cells towards IgA1 and IgA2.
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 approximately 10% of CD40-activated naive sIgD+ B cells. In the presence of IL-10 and TGF-beta, 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-beta. 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-beta. 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.
Fayette
J
J
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Dubois
B
B
Vandenabeele
S
S
Bridon
J M
JM
Vanbervliet
B
B
Durand
I
I
Banchereau
J
J
Caux
C
C
Brière
F
F
D018952:Antigens, CD34; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching; D016753:Interleukin-10 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000032:analysis / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D018952:Antigens, CD34; D019013:CD40 Antigens; D007070:Immunoglobulin A; D011947:Receptors, Antigen, B-Cell; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013936:Thymidine