What are basophils?

Basophils are the rarest and least characterized of the granulocyte subtypes and represent fewer than 1% of circulating leukocytes.  They share many functional similarities with mast cells, including expression of high-affinity IgE receptors, and secretion of histamine upon activation (Figure 1). Contrastingly, they are present almost exclusively in circulation, while mast cells are more likely to be tissue-resident. Basophils are the only circulating leukocytes that contain histamine and secrete certain cytokines including IL-4.

Basophil development

Originally believed to be circulating precursors of mast cells that migrate to tissues for maturation, basophils are now understood to be a distinct hematopoietic lineage that originates in the bone marrow. While it is understood that they arise from progenitor cells within the granulocyte/monocyte progenitor population, the exact mechanisms of basophil differentiation and development remain poorly characterized. In vitro mouse studies of basophils show that IL-3 and TSLP can both drive basophil differentiation from progenitor cells independently of one another and that there are phenotypic differences between the cells derived in response to these cytokines.  However, both IL-3 and TSLP have also been shown to be dispensable for basophil development, further demonstrating that our understanding of the basophil development pathway remains incomplete.

Basophil effector function

Basophils express the high affinity IgE receptor (FcεRI), which binds the Fc region of the IgE immunoglobulin secreted in response to parasitic infections and allergens.  Cross-linking of IgE with the IgE receptor (FcεRI) on the basophil surface results in basophil degranulation and release of inflammatory mediators.  The immediate degranulation results in release of inflammatory mediators such as histamine, a vasodilator that promotes blood flow to tissues and drives the swelling, pain, and redness of an inflammatory lesion, and proteases.  Later secretions include newly synthesized cytokines, chemokines, and leukotrienes such as LTC4 (Leukotriene C4), which are lipid mediators of inflammation.

Basophils play a key role in the type 2 immune responses to ectoparasite infections, such as ticks and helminth worms.  Basophils are thought to be a significant source of IL-4 and IL-13 under these conditions, which are important drivers of Th2 T cell and M2 macrophage differentiation. The type 2 responses mediated by basophils and the cells that they activate contribute to parasite clearance and host defense.  Furthermore, a potential role for basophils as antigen-presenting cells has been suggested but is still under investigation.  A diagram of additional basophil activating receptors and secretions can be seen in Figure 2.  As basophils share many overlapping functions with mast cells, a diagram of similarities and differences can be found in Figure 1.

Basophils in allergy and autoimmunity

Basophils are implicated in a variety of allergic responses, and their accumulation is observed in allergies of the skin, gastrointestinal tract, and respiratory system.  The secretion of IL-4 by infiltrating basophils is thought to be one of the factors driving Th2 cell-mediated inflammation in these conditions. Basophil depletion is demonstrated to ameliorate allergic inflammation in mouse models, and anti-IgE therapy has been used for treatment of some allergic disorders in humans.  The specific role of basophils in allergy has yet to be clearly defined, as it has long been believed that mast cells play a greater role in the acute responses due to their residence in affected tissues.  However, the ability of basophils to drive allergy promoting Th2 responses is potentially a key contributing factor to the late-phase allergic inflammation.

Basophil activation is observed in some autoimmune disorders, including systemic lupus erythematosus and inflammatory bowel disorders.  Basophil accumulation is observed at the sites of inflammation, where cells display upregulation of CD203c, an indicator of activation and degranulation.  Basophils are thought to contribute to the pathogenesis of these diseases by augmenting Th2 responses and via release of histamine and other effector molecules.

Flow cytometry analysis of basophils

Under homeostatic conditions, basophils are most prevalent circulating in the periphery, making flow cytometry a convenient tool for their characterization.  A list of relevant immunophenotyping markers can be found in Table 1. Murine basophils can also be cultured from bone marrow in the presence of either IL-3 or TSLP, although the conditions of culture have been observed to give rise to phenotypic and functional differences in the resultant cells.

Basophil activation and degranulation can also be investigated by flow cytometry using the Basophil Activation Test (BAT), which measures the capacity of IgE to activate basophils in the presence of experimental antigens.  In the BAT, basophils, often as part of a mixed cell population in whole blood, are exposed to potential allergens, then analyzed for upregulation of activation markers by flow cytometry in comparison to unstimulated cells.  While a variety of markers or signaling proteins can be used for this analysis, CD63 and CD203c are commonly used and believed to be representative of degranulation.  Clinical applications for the BAT include diagnosis of food and other environmental allergies, investigation of potential drug allergies, and study of the mechanisms of basophil function.

Table 1: Non-exhaustive list of basophil markers

Cell subtypeMarkerLocalizationSpecies
Pan-granulocytesCD11bSurfaceHuman and mouse
BasophilsIL3Ra (CD123)SurfaceKey phenotyping marker: Human and mouse
IL-4SecretedHuman and mouse
FceR1SurfaceKey phenotyping marker
IL-13SecretedHuman and mouse
HistamineSecretedHuman and mouse
CCL3 (MIP-1 alpha)SecretedHuman and mouse
CD9SurfaceHuman and mouse
CD11aSurfaceHuman and mouse
CD13SurfaceHuman and mouse
CD25SurfaceHuman and mouse
CD33SurfaceHuman and mouse
CD38SurfaceHuman and mouse
CD43SurfaceHuman and mouse
CD63SurfaceHuman and mouse
CD88 (C5a receptor)SurfaceHuman and mouse
CD125SurfaceHuman and mouse
CD154 (CD40 ligand)SurfaceHuman and mouse
CD192 (CCR2)SurfaceHuman and mouse
CD218 (IL-18R)SurfaceHuman and mouse
CD282 (TLR2)SurfaceHuman and mouse
CD284 (TLR4)SurfaceHuman and mouse
CD286 (TLR6)SurfaceHuman and mouse
CD294 (CRTH2)SurfaceHuman and mouse
CD281 (TLR1)IntracellularHuman and mouse
CD289 (TLR9)IntracellularHuman and mouse
C/EBP alphaIntracellularHuman and mouse
GATA-2IntracellularHuman and mouse


Figure 3: Identification of human basophils cells using flow cytometry and basophil cellular marker, 2D7. 2D7 is an antigen expressed exclusively by human basophils. 2D7 is a 7.2–7.5 kDa protein present exclusively in the secretory granules of human basophils. Upon activation, basophils may degranulate, thereby decreasing the amount of 2D7 antigen available for staining. Normal human peripheral blood cells were surface stained with Anti-Human CD123 APC (Cat. No. 17-1239-42). The cells were then permeabilized with the Intracellular Fixation and Permeabilization Buffer Set (Product # 88-8824) and intracellularly stained with Mouse IgG1 K Isotype Control PE (Cat. No. 12-4714-82) (left) or Anti-2D7 (Human Basophil Marker PE) (Cat. No. 12-9748-42) (right). This antibody does not stain mast cells. Cells in the lymphocyte gate were used for analysis.

Related articles and resources


Mast Cell Overview
Learn about mast cells and how they share similarities with basophils.

For Research Use Only. Not for use in diagnostic procedures.