The ability of monocyte to differentiate into different cells types is a well known phenomenon. For example, monocytes differentiate into dendritic cells (mDCs) in response to Granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 while GM-CSF alone induces monocytes to differentiate into macrophages, as well as to different types of macrophages according to the culture conditions. This plasticity has made monocyte a very useful tool for the understanding of the cellular and molecular mechanism underlying the immune response. While attempting to generate an in vitro system simulating a germinal center microevironment, we have observed the generation of large adherent dendritic-like cells in the cell culture of unique morphological appearance. The cells are large in size, most over 30 µm, having spingle-shape morphology and long pseudopodias. We have found that the cells originate from CD14+ monocytes. We also found that differentiation of monocytes into this type of cells was mediated by the presence of Follicular Helper (TFH) cells in the culture. Furthermore, the result of transwell experiments show that cell-cell contact was not required. Since secretion of IL-21 is kwon to be one of the function TFH cells we tested the effect of this cytokine on mDC differentiation. We found that IL-21 alone was capable of differentiating purified CD14+ monocytes into this type of dendritic cells, which are morphologically distinct to the traditional mDC or macrophages. To date we haven't been able to conclusively define the identity of these cells, however, current genetic and phenotype profiling should help us to define the nature and possible function of these cells.