Critical role of IL-12 in dendritic cell-induced differentiation of naive B lymphocytes.
Dendritic cells (DC) are potent APCs initiating immune responses. In a previous report, we demonstrated that DC directly enhance both proliferation and differentiation of CD40-activated naive and memory B cells. The present study deciphers the molecular mechanisms involved in DC-dependent regulation of B cell responses. Herein, we have identified IL-12 as the mandatory molecule secreted by CD40-activated DC that promote the differentiation of naive B cells into plasma cells secreting high levels of IgM. In fact, IL-12 synergizes with soluble IL-6R alpha-chain (sgp80), produced by DC, to drive naive B cell differentiation. IL-12 is critical for the differentiation of naive B cells into IgM plasma cells, whereas IL-6R signaling mainly promotes Ig secretion by already differentiated B cells. The differentiation of naive B cells in cocultures of B cells, T cells, and DC is IL-12 dependent, definitely demonstrating that the role of DC in humoral responses is not confined to the activation of T cells and further extending the physiologic relevance of DC/B cell interaction. Finally, this study also identifies differential requirements for DC-dependent naive and memory B cell differentiation, the latter being IL-12 independent. Altogether these results indicate that, in addition to prime T cells toward Thl development, DC, through the production of IL-12, may also directly signal naive B cell during the initiation of the immune response.
Dubois
B
B
Laboratory for Immunological Research, Schering Plough, Dardilly, France.
Massacrier
C
C
Vanbervliet
B
B
Fayette
J
J
Brière
F
F
Banchereau
J
J
Caux
C
C
D019138:Antibodies, Blocking / Q000494:pharmacology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004357:Drug Synergism; D005312:Fetal Blood; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000502:physiology; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000276:immunology / Q000502:physiology; D012995:Solubility
D019138:Antibodies, Blocking; D019013:CD40 Antigens; D007106:Immune Sera; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D019947:Receptors, Interleukin-6; D018664:Interleukin-12