Mast cell-committed progenitors

Mast cells play a central role in the development of the immediate hypersensitivity reaction. This reaction occurs within minutes after the recognition of an antigen by IgE antibodies bound to mast cells in sensitized individuals. Although diseases based on the immediate hypersensitivity reaction, such as allergic rhinitis, bronchial asthma, and allergic gastroenteritis, are quite common and are even increasing in prevalence in industrialized countries, the development of mast cells has been investigated by relatively few researchers. During the first 100 years after Paul Ehrlich discovered them, mast cells were believed to be a component of connective tissue that was derived from undifferentiated mesenchymal cells. Furthermore, it was believed that mast cells functioned and died within connective tissue. However, in the 1980s, in vivo and in vitro evidence emerged that mast cells were the progeny of hematopoietic stem cells (HSCs) (1, 2). Unlike most HSC offspring like erythrocytes, platelets, and neutrophils, which complete their differentiation within the bone marrow, mast cells complete differentiation in connective tissue (3). Most physicians are aware that morphologically identifiable mast cells are not present in the peripheral blood circulation, but an appreciable portion of them believe that basophils may become mast cells after invading connective tissue. This discrepancy has arisen because the origin of mast cell-committed progenitors (MCPs) was unknown until now. The work of Chen et al . (4) in this issue of PNAS has identified MCPs in the bone marrow of adult mice. The authors clearly demonstrate that MCPs do not contain basophilic granules, …