Blood Journal
Leading the way in experimental and clinical research in hematology
IMMUNOBIOLOGY

What does a basophil do?

  1. Cem Akin
  1. UNIVERSITY OF MICHIGAN

The absence of an animal model deficient in basophils has been a major obstacle in efforts to delineate the functional significance of basophils in health and disease. In this issue of Blood, Obata and colleagues describe a monoclonal antibody (Ba103) which selectively reduces the number of basophils in the peripheral blood and spleen in mice.

Basophils and mast cells share significant phenotypic and functional properties (see figure).1 Both cell lineages possess metachromatic granules containing histamine and proteoglycans, and express the high-affinity immunoglobulin E (IgE) receptor through which they can be activated to degranulate and synthesize inflammatory mediators. These similarities have led many to consider these 2 cell types to have redundant functional properties. Experiments performed on mast-cell–deficient mice confirmed not only the essential role of mast cells in allergic inflammation, but also revealed their important contributions to a number of innate and acquired immune responses.2,3 However, while mast-cell function in vivo can be studied by using mice displaying defective expression of KIT due to loss-of-function mutations in c-kit, a similar model has not been available for basophils. Development of the Ba103 antibody, which specifically depletes basophils, should therefore facilitate a more complete understanding of the functional significance of this cell lineage.

Photomicrograph of a human bone marrow mast cell (left) and a peripheral-blood basophil (right) stained with Wright-Giemsa. Images were acquired using an Olympus BX41 microscope equipped with a Planar 100×/1.25 oil lens and an Olympus Q Color 3 camera (Olympus America, Melville, NY) and were processed with Q Capture Pro version 5.1.1.14 software and Microsoft PowerPoint 2002 (Microsoft, Redmond, WA).

A critical question pertinent to the study by Obata and colleagues, as raised by a recent commentary in Blood,4 is whether the cells recognized and depleted by Ba103 antibody are really basophils. Ba103 recognizes a subset of mast cells as well as a second cell type that is increased by infection with the parasite Nippostrongylus brasiliensis, carries high-affinity receptors for IgE and IL-3 while lacking other lineage commitment markers, has the ultrastructural features of basophils, and expresses the basophil protease MMCP-8 while lacking other proteases characteristically associated with eosinophils and neutrophils. It therefore seems reasonable to accept the latter cell type recognized by the antibody as a basophil. When injected intravenously, the antibody selectively depletes basophils but not mast cells.

The experiments reported by Obata and colleagues, which compare and contrast mast-cell–deficient and basophil-deficient mice, reveal interesting clues about the contribution of basophils to various allergic reactions. Basophils have been suspected to contribute to IgE-mediated immediate hypersensitivity reactions including anaphylaxis. Interestingly, the authors show that, in contrast to mast-cell–deficient mice, basophil-deficient mice display no significant suppression of IgE-mediated systemic or local anaphylaxis. Perhaps less surprisingly, basophil-deficient mice also do not have any significant inhibition of delayed contact hypersensitivity.

Basophils have been considered to be important mediators of late-phase allergic reactions, based on their having been found in increased numbers after allergen challenge in tissues such as lung and skin.5 Experiments by Obata and colleagues suggest that basophils play a more pivotal role in initiation rather than maintenance of IgE-mediated chronic inflammation, at least in the skin. Human counterparts of IgE-mediated chronic inflammatory processes may include such common disorders as atopic dermatitis and allergic asthma. The value of basophils as targets for future novel therapies for selected allergic disorders remains to be explored.

Finally, it could be predicted that the availability of a basophil-deficient animal model should lead to studies dissecting the role of basophils in innate immunity and other nonallergic inflammatory processes, ultimately shedding more light on the age old question of what a basophil does to contribute to healthy immunologic homeostasis.

Footnotes

  • Conflict-of-interest disclosure: The author declares no competing financial interests. ■

REFERENCES