Fibroblasts support outgrowth of splenocytes simultaneously expressing B lymphocyte and macrophage characteristics.
B lymphocytes and macrophages are considered to be derived from separate lineages and to have specialized functions. However, some malignant B lymphocytes can generate descendants with macrophage-like properties and monocytoid B cells are described in certain diseases. In this report, we demonstrate that normal biphenotypic cells can be isolated by incubating mouse splenic fibroblasts or their conditioned media with purified splenic B lymphocytes. Phagocytic vascular cells were isolated that simultaneously displayed typical B cell (B220, surface IgM, surface IgD, and CD5) and macrophage (F4/80 and Mac-1) markers and contained rearranged Ig genes. F(ab')2 anti-mu Ab inhibited the proliferation of these biphenotypic cells in a dose-dependent manner, indicating that functional IgM was expressed. The adherent B/macrophage cells also displayed CD40 and BCL-2 and were sensitive to ionizing radiation, consistent with having a B cell origin. In the presence of splenic fibroblast-conditioned medium, lines of B/macrophage cells can be propagated for months in vitro. The ability to derive these biphenotypic cells from normal sources suggests that certain B lymphocytes and macrophages share a closer lineage relationship than is predicted by current models of hematopoietic differentiation. Alternatively, these biphenotypic cells may represent a primitive B lymphocyte lineage that possesses greater flexibility to adapt to infectious agents than dedicated lymphoid or myeloid cells and may be prone to malignant transformation.
Borrello
M A
MA
Cancer Center, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Phipps
R P
RP
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002469:Cell Separation; D005347:Fibroblasts / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D051381:Rats; D013154:Spleen / Q000166:cytology*
D015415:Biomarkers