Recent studies have suggested that the accessory molecules B7.1 (CD80) and B7.2 (CD86) differ in their capacity to generate Th1 vs Th2 responses. Atopic dermatitis (AD) is a chronic allergic skin disease associated with increased IgE synthesis. To determine the potential role of B7.2 molecules in AD, the present study was conducted to compare the expression of B7.1 vs B7.2 on B cells from patients with AD vs normal subjects or patients with psoriasis. The expression of B7.2 on B cells of AD patients (53.67 +/- 3.10%) was significantly higher than normals (38.02 +/- 4.95%; p = 0.02) and psoriasis patients (40.19 +/- 2.70%; p = 0.006). In contrast, there was no significant difference in B7.1 expression among the three subject groups. Interestingly, total serum IgE from AD patients and normal subjects correlated significantly with B7.2 expression on B cells (r = 0.68; p = 0.004), suggesting a role for B7.2+ B cells in IgE synthesis. Indeed, purified B7.2+ B cells produced significantly more IgE than B7.2- B cells in vitro (p = 0.04). Anti-human B7.2, but not B7.1, mAb significantly (p < 0.05) decreased IgE production by PBMC stimulated with IL-4 and anti-CD40 mAb. Furthermore, B7.2+ B cells had a significantly higher level of IL-4R and CD23 expression than B7.1+ B cells. These data demonstrate the predominant expression of B7.2 in AD, but not psoriasis, and a novel role for this molecule in IgE synthesis.