Fibroblast-secreted macrophage colony-stimulating factor is responsible for generation of biphenotypic B/macrophage cells from a subset of mouse B lymphocytes

Normal and malignant CD5(+) B lymphocytes can develop macrophage-like chara cteristics. One stimulus of this phenotypic shift is culture of normal mous e splenic B lymphocytes with splenic fibroblasts or their conditioned media . These biphenotypic B/macrophage (B/M phi) cells simultaneously display ma crophage characteristics, such as phagocytosis and F4/80 expression, while retaining B cell features, including expression of surface Ig, CD5, B220, a nd rearranged Ig genes. The present study investigated the fibroblast-secre ted factor that promotes this phenotypic change from B cell to B/M phi cell . RT-PCR analysis demonstrated that mRNA for M-CSF is produced by splenic f ibroblasts, Recombinant M-CSF (CSF-1) could replace fibroblast-conditioned medium to elicit the development and survival of B/M phi cells from splenic B lymphocytes. In addition, neutralization of fibroblast-secreted M-CSF wi th specific mAbs abrogated the ability of conditioned supernatants to promo te outgrowth of B/M phi cells. The transition from B lymphocyte to B/M phi cell was marked by the kinetic appearance of mRNA for the M-CSF receptor, c -fms, at day 3 following culture initiation. These results demonstrate that M-CSF is important in the development and physiology of mouse B/M phi cell s and potentially in the growth of human biphenotypic hematological maligna ncies. Interestingly, the presence of IFN-gamma in splenic B lymphocyte cul tures abrogated the effect of fibroblast-conditioned medium or M-CSF on out growth of B/M phi cells. Furthermore, these findings suggest that a Th1 mic roenvironment favored by typical macrophages is detrimental to the outgrowt h of B/M phi cells.