Critical role of IL-12 in dendritic cell-induced differentiation of naive B lymphocytes.
J Immunol
; 161(5): 2223-31, 1998 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-9725215
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dendritic Cells
/
B-Lymphocyte Subsets
/
Interleukin-12
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Immunol
Year:
1998
Document type:
Article
Affiliation country:
France