The monoclonal antibody 97A6 defines a novel surface antigen expressed on human basophils and their multipotent and unipotent progenitors

Basophils (Ba) and mast cells (MC) are important effector cells of inflamma tory reactions. Both cell types derive from CD34(+) hematopoietic progenito rs. However, little is known about the cell subsets that become committed t o and give rise to Ba and/or MC. We have generated a monoclonal antibody (M oAb), 97A6, that specifically detects human Ba, MC (lung, skin), and their CD34(+) progenitors. Other mature hematopoietic cells (neutrophils, eosinop hils, monocytes, lymphocytes, platelets) did not react with MoAb 97A6, and sorting of 97A6(+) peripheral blood (PB) and bone marrow (BM) cells resulte d in an almost pure population (>98%) of Ba. Approximately 1% of CD34(+) BM and PB cells was found to be 97A6(+). Culture of sorted CD34(+)97A6(+) BM cells in semisolid medium containing phytohemagglutinin-stimulated leukocyt e supernatant for 16 days (multilineage assay) resulted in the formation of pure Ba colonies (10 of 40), Ba-eosinophil colonies (7 of 40), Ba-macropha ge colonies (3 of 40), and multilineage Ba-eosinophil-macrophage and/or neu trophil colonies (12 of 40). In contrast, no Ba could be cultured from CD34 (+)97A6(-) cells. Liquid culture of CD34(+) PB cells in the presence of 100 ng/mL interleukin (IL)-3 (Ba progenitor assay) resulted in an increase of 97A6(+) cells, starting from 1% of day-0 cells to almost 70% (basophils) af ter day 7. Culture of sorted BM CD34(+)97A6(+) cells in the presence of 100 ng/mL stem cell factor (SCF) for 35 days (mast cell progenitor assay) resu lted in the growth of MC (>30% on day 35). Anti-IgE-induced IgE receptor cr osslinking on Ba for 15 minutes resulted in a 4-fold to 5-fold upregulation of 97A6 antigen expression. These data show that the 97A6-reactive antigen plays a role in basophil activation and is expressed on multipotent CD34() progenitors, MC progenitors, Ba progenitors, as well as on mature Ba and tissue MC. The lineage-specificity of MoAb 97A6 suggests that this novel ma rker may be a useful tool to isolate and analyze Ba/MC and their progenitor s. (C) 1999 by The American Society of Hematology.