Fibroblasts support outgrowth of splenocytes simultaneously expressing B lymphocyte and macrophage characteristics.

Abstract

Abstract 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.