[IgM+IgD+CD27+ B cells in human: an essential role in the protection against encapsulated bacteria]

In humans, CD27+ blood B cells with mutated immunoglobulin (Ig) receptors comprise two major populations: isotype-switched memory cells (IgG+ or IgA+CD27+) and IgM+IgD+CD27+ cells. While switched CD27+ cells are generated in germinal centers (GC) by T-dependent (TD) responses, the origin of IgM+IgD+CD27+ cells is still controversial. Data including ours support the view that these cells can develop and mutate along a GC-independent pathway and that they represent circulating marginal zone B (MZB) cells involved in T-independent (TI) responses. Our data provide evidence for a developmental diversification of these MZB cells, at least in very young children, outside of TD and TI immune responses. The identification of a human MZB cell precursor with NOTCH2-dependent differentiation properties further argue in favor of the existence of a MZB cell lineage in humans, like in rodents. At last, a role for Toll-like receptors in the development and/or maintenance of IgM+IgD+CD27+ B cells is proposed.