Affiliation:
1. *Medicine,
2. †Pediatrics, and
3. §Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital; and
4. ‡Pathology, Harvard Medical School;
5. ¶Partners Asthma Center, Boston, MA 02115
Abstract
Abstract
Tissue mast cell development requires stem cell factor (SCF), whereas helminth-induced intestinal mucosal mast cell hyperplasia also requires T cell-derived factors such as IL-3. We generated progenitor mast cells (PrMC) from mouse bone marrow cells (BMC) in vitro with a triad of SCF, IL-6, and IL-10 that exhibit IL-3-mediated mitogenic and maturation responses. SCF/IL-6/IL-10 transiently elicited a cell subpopulation with the phenotype (c-kithighThy-1low) of fetal blood promastocytes at 3 wk of culture that progressed within 1 wk to FcεRI-bearing PrMC, designated PrMCTriad. PrMCTriad lacked mouse mast cell carboxypeptidase A (mMC-CPA) protein, required SCF for IL-3-driven thymidine incorporation, and responded to SCF plus IL-3 with strong mMc-CPA immunoreactivity, clarifying distinct sequential roles for SCF and IL-3 in mast cell development. PrMCTriad, arising from BMC through promastocytes, are metamastocytes that acquire microenvironmentally determined phenotypic features.
Publisher
The American Association of Immunologists
Subject
Immunology,Immunology and Allergy