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Laboratory for Immunological Research, Schering Plough, Dardilly, France
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 
-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 Th1 development, DC, through the production of
IL-12, may also directly signal naive B cell during the initiation of
the immune response.
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