Background Numerous data obtained by different research laboratories indicate that specific IgE production is triggered independently of specific IgG or IgA ones and so it is not linked to fully matured germinal centers formation in the secondary lymphoid organs. The aim of this study was to clarify whether specific IgE production is triggered by low antigen doses administrated in tertiary tissues enriched by lymphoid structures. Methods Ovalbumin (OVA) in different doses (100 ng to 10 μg) was administrated three times a week for 4–5 weeks intraperitoneally (i.p.) or subcutaneously (s.c.) to female BALB/c mice in the wither region which is enriched in fat-associated lymphoid clusters or in the foot pad region not containing them. Results OVA-specific IgE was predominantly induced by low but not high antigen doses and only after immunization into the withers. IgE isotype switching was triggered exclusively in the withers adipose tissue but not in the regional lymph nodes while mature IgE expressing cells were observed both in the withers and lymph nodes. Anti-proliferative genotoxic stress inducing drugs shifted the balance from IgG1 towards IgE production. Conclusions Tertiary lymphoid structures possess unique environment where B-cell antibody isotype switching to IgE predominantly occurs. This phenomenon is partially explained by hampered proliferation of B-cells in these structures.