Hematopoiesis: The Role of Stromal Integrin Interactions in Pro-B Cell Proliferation.
Recent studies using long term bone marrow cultures have concluded that adherence of lymphoid precursors to the underlying stromal cells is required for normal B cell development. However, the function of specific integrin interactions in B cell development remains unresolved. In our laboratory, we observed that maximal proliferation of pro-B cells required the presence of stromal cells and that stromal cytokines alone could not replace the requirement for stromal cell contact. For that reason, we questioned whether integrin interactions play a role in regulating pro-B cell proliferation in the bone marrow. Murine pro-B cell line Cl.92 expressed VLA-4, CD44, and fibronectin-receptor. Abrogation of binding of these molecules to stromal cell ligands using blocking antibodies resulted in failure of pro-B cell adherence and significant decreases in pro-B cell proliferation. Disruption of single integrin interactions did not compromise either adhesion of pro-B cells to stromal cells or IL-7 stimulated proliferation. Taken together, these data suggest that normal pro-B cells interact with stromal cells through multiple integrin interactions and that integrin mediated potentiation of pro-B cell proliferation is functionally redundant and not affected by failure of single ligand interactions.
Hahn
BRANDI K.
BK
Blood and Marrow Transplantation Program of the Mary Babb Randolph Cancer Center.
Piktel
DEBRA
D
Gibson
LAURA F.
LF
Landreth
KENNETH S.
KS