Adjuvant Effect of Benzo(a)pyrene on Specific IgE Production and B-Cell Subpopulations in Lungs, Regional Lymph Nodes, and Spleen in Mouse Allergy Model

Abstract

Objective: Despite a large number of works focused on the search for the mechanisms of formation of IgE-producing B-cells, the question of the relative contribution of germinal centers and extrafollicular foci B-cells in this process still remains controversial. Of particular interest is the study of the mechanisms of stimulation of the allergic immune response under the influence of air pollutants. The aim of the work was to study the connection between the adjuvant effect of benzo(a)pyrene (BaP) on the production of specific IgE in a novel low-dose allergy model with changes in the subpopulation composition of B-cells in the tissue of the immunization site and secondary lymphoid organs. Methods: Antigen without any stimuli was administrated to one group of BALB/c mice for 9 weeks in a low (0.3 μg) dose. BaP was administrated to another group of mice along with antigens at a dose of 4 ng. B-cell subpopulations were analyzed by flow cytometry. Results and discussion: BaP significantly stimulated the production of allergen-specific IgG₁ at early (3 weeks) time point, and allergen-specific IgE at late (9 weeks) time point. The aeropollutant increased the content of CD19⁺CD38^–CD95⁺B220⁺ germinal center B-cells with the phenotype and their precursors (CD19⁺CD38⁺CD95⁺B220⁺) with the phenotype in the spleen at early and late time points, but not in the lungs or regional lymph nodes. Under its influence, the content of CD19⁺CD38^–CD95⁺B220^– and CD19⁺CD38⁺CD95⁺B220⁺ extrafollicular plasmablasts in the spleen at an early time point and in lung tissue at a later time point also increases. In the spleen, BaP increased the content of CD138⁺CD19^–B220⁺ and CD138⁺CD19^–B220^– mature plasma cells, and in regional lymph nodes the content of CD138⁺CD19⁺B220^– immature plasma cells at a later time point. Conclusions: The adjuvant effect of BaP on the production of specific IgE was largely associated with stimulation of the formation of germinal centers in the spleen and with extrafollicular activation of B-cells in lung tissue.