607:
Cat dander extract directly stimulates BAFF-dependent class switch recombination to IgE in B cells without T-cell help
Sunday, March 4, 2018: 3:00 PM
S230AB (Convention Center)
Toshiko Itazawa, MD PhD, ,
RATIONALE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.