The innate factors that stimulate allergen-induced class switch recombination (CSR) to IgE in entopy or local allergic rhinitis are largely unknown. Cat dander extract (CDE) directly stimulates B cells CSR to IgE through a Myd88-dependent signaling mechanism in the presence of IL-4 and T-cell help (AAAAI abstract 2017). Here we hypothesized that CDE can provide an innate signal that directly stimulates B cell-activating factor of TNF family (BAFF)-dependent CSR to IgE in naïve B-cell without T-cell help.
hTERT immortalized normal human bronchial epithelial cells (HBEC) were stimulated with CDE and mRNA expression of Baff was quantified. Purified splenocyte-derived B cells from naïve wild type (WT) C57BL/6 mice or Myd88 KO mice were cultured with CDE in the presence of IL-4 and/or BAFF. Total IgE and IgE CSR associated gene were evaluated. CDE had less than 0.1pg endotoxin per µg protein.
The stimulation with CDE increased the mRNA expression of BAFF in HBEC. In the presence of IL-4 and BAFF, CDE stimulated IgE secretion and increased mRNA expression of CSR-inducing genes such as Irf4, Aicda, PSTε, Id2, GLε, and GLγ in cultured WT but not Myd88 KO B cells.
CDE provides a crucial MyD88-dependent signal that directly stimulates CSR in BAFF+IL-4-stimulated B-cells to IgE without T-cell help. These results suggest that local nasal CSR to IgE in subjects with entopy or local allergic rhinitis.may result from cat dander-induced BAFF secretion from nasal epithelial cells together with direct stimulation of local B cells through MyD88-dependent TLRs.