Modulating the Human Basophil Phenotype During Its Development and Maturation: Basophils Derived from In Vitro Cultures of CD34⁺ Progenitor Cells

Abstract

Historically, the human basophil that is studied experimentally comes from peripheral blood. But there is evidence that only a short portion of the basophil life cycle related to IgE-mediated function occurs in the blood. The same evidence suggests that IgE-mediated functionality is present for 5–7 days in the bone marrow (or other tissues) during which the cell modulates its phenotype according to local conditions. It is suggested that to properly understand the nature of basophil behavior, a better understanding of its biology during maturation would be helpful. For example, one highly suggestive line of evidence for the relevance of understanding the maturation period is related to the change in basophil phenotype that occurs during treatment of patients with omalizumab. During this treatment, the intrinsic reactivity or sensitivity of the basophils is significantly increased despite, or perhaps because of, the dramatic reduction in FcεRI expression that accompanies this treatment. One of the critical signaling enzymes to increase expression selectively in basophils during treatment is SYK, which is one of the earliest signaling tyrosine kinases involved in translating the aggregation of FcεRI into secretion from the cell. Treatment with omalizumab increases SYK expression, and this observation focuses some attention of how SYK expression is regulated. It is possible that the key regulation occurs during maturation of the basophil. Regardless of the mechanisms operative in this particular treatment, understanding the process of maturation and the extrinsic factors that influence it may lead to better understanding of disease processes. Therefore, this chapter will discuss and present techniques to work with maturing human basophils.