CD4 and diabetes mellitus: It has been demonstrated that B-1 cells down-regulate macrophage functions in vitro[14], induce macrophage polarization to an alternative phenotype [13], modulate T cell infiltration into allografts [4] and into the pancreas in mice that spontaneously develop diabetes [20], induce the differentiation of CD4+ T cells to become pro-inflammatory Th17 cells [21] and also have a tolerogenic function in a model of allergic reaction [22].