J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/01/341/10 $2.00
Volume 185 January 1997 341-350

CD40 Ligation on Human Cord Blood CD34⁺ Hematopoietic Progenitors Induces Their Proliferation and Differentiation into Functional Dendritic Cells

By Leopoldo Flores-Romo, Pia Björck, Valérie Duvert, Cees van Kooten, Sem Saeland, and Jacques Banchereau

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

Human CD34⁺ multilineage progenitor cells (CD34HPC) from cord blood and bone marrow express CD40, a member of the tumor necrosis factor-receptor family present on various hematopoietic and nonhematopoietic cells. As hyper-IgM patients with mutated CD40 ligand (CD40L) exhibit neutropenia, no B cell memory, and altered T cell functions leading to severe infections, we investigated the potential role of CD40 on CD34HPC development. CD40activated cord blood CD34HPC were found to proliferate and differentiate independently of granulocyte/macrophage colony-stimulating factor, into a cell population with prominent dendritic cell (DC) attributes including priming of allogeneic naive T cells. DC generated via the CD40 pathway displayed strong major histocompatibility complex class II DR but lacked detectable CD1a and CD40 expression. These features were shared by a dendritic population identified in situ in tonsillar T cell areas. Taken together, the present data demonstrate that CD40 is functional on CD34HPC and its cross-linking by CD40L⁺ cells results in the generation of DC that may prime immune reactions during antigen-driven responses to pathogenic invasion, thus providing a link between hematopoiesis, innate, and adaptive immunity.

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