DEPs Induce Local Ige Class Switching Independent of Their Ability to Stimulate iBALT de Novo Formation.

BACKGROUND: Diesel exhaust particles (DEPs) are leading to a general increase in atopic diseases worldwide. However, it is still unknown whether DEPs induce systemic B-cell IgE class switching in secondary lymphoid organs or locally in the lungs in inducible bronchus-associated lymphoid tissue (iBALT). The aim of this work was to identify the exact site of DEP-mediated B-cell IgE class switching and pro-allergic antibody production. METHODS: We immunized BALB/c mice with different OVA doses (0.3 and 30 µg) intranasally in the presence and absence of two types of DEPs, SRM1650B and SRM2786. We used low (30 µg) and high (150 µg) DEP doses. RESULTS: Only a high DEP dose induced IgE production, regardless of the particle type. Local IgE class switching was stimulated upon treatment with both types of particles with both low and high OVA doses. Despite the similar ability of the two standard DEPs to stimulate IgE production, their ability to induce iBALT formation and growth was markedly different upon co-administration with low OVA doses. CONCLUSIONS: DEP-induced local IgE class switching takes place in preexisting iBALTs independent of de novo iBALT formation, at least in the case of SRM1650B co-administered with low OVA doses.

Early IgE Production Is Linked with Extrafollicular B- and T-Cell Activation in Low-Dose Allergy Model.

Despite its paramount importance, the predominant association of early IgE production with harmless antigens, via germinal-center B- and T-cell subpopulations or extrafollicular activation, remains unresolved. The aim of this work was to clarify whether the reinforced IgE production following the subcutaneous immunization of BALB/c mice with low antigen doses in withers adipose tissue might be linked with intensified extrafollicular or germinal-center responses. The mice were immunized three times a week for 4 weeks in the withers region, which is enriched in subcutaneous fat and tissue-associated B cells, with high and low OVA doses and via the intraperitoneal route for comparison. During long-term immunization with both low and high antigen doses in the withers region, but not via the intraperitoneal route, we observed a significant accumulation of B220-CD1d-CD5-CD19+ B-2 extrafollicular plasmablasts in the subcutaneous fat and regional lymph nodes but not in the intraperitoneal fat. Only low antigen doses induced a significant accumulation of CXCR4+ CXCR5- CD4+ extrafollicular T helpers in the withers adipose tissue but not in the regional lymph nodes or abdominal fat. Only in subcutaneous fat was there a combination of extrafollicular helper accumulation. In conclusion, extrafollicular B- and T-cell activation are necessary for early IgE class switching.