Type I IFN Receptor Signaling on B Cells Promotes Antibody Responses to Polysaccharide Antigens.
Journal Article (Journal Article)
We previously reported monophosphoryl lipid A (MPL) and synthetic cord factor trehalose-6,6'-dicorynomycolate (TDCM) significantly increase Ab responses to T cell-independent type 2 Ags (TI-2 Ags) in a manner dependent on B cell-intrinsic TLR4 expression, as well as MyD88 and TRIF proteins. Given the capacity of MPL to drive type I IFN production, we aimed to investigate the extent to which type I IFN receptor (IFNAR) signaling was required for TI-2 responses and adjuvant effects. Using Ifnar1-/- mice and IFNAR1 Ab blockade, we found that IFNAR signaling is required for optimal early B cell activation, expansion, and Ab responses to nonadjuvanted TI-2 Ags, including the pneumococcal vaccine. Further study demonstrated that B cell-intrinsic type I IFN signaling on B cells was essential for normal TI-2 Ab responses. In particular, TI-2 Ag-specific B-1b cell activation and expansion were significantly impaired in Ifnar1-/- mice; moreover, IFNAR1 Ab blockade similarly reduced activation, expansion, and differentiation of IFNAR1-sufficient B-1b cells in Ifnar1-/- recipient mice, indicating that B-1b cell-expressed IFNAR supports TI-2 Ab responses. Consistent with these findings, type I IFN significantly increased the survival of TI-2 Ag-activated B-1b cells ex vivo and promoted plasmablast differentiation. Nonetheless, MPL/TDCM adjuvant effects, which were largely carried out through innate B cells (B-1b and splenic CD23- B cells), were independent of type I IFN signaling. In summary, our study highlights an important role for B-1b cell-expressed IFNAR in promoting responses to nonadjuvanted TI-2 Ags, but it nonetheless demonstrates that adjuvants which support innate B cell responses may bypass this requirement.
- Spurrier, MA; Jennings-Gee, JE; Haas, KM
- January 2023
Volume / Issue
- 210 / 2
Start / End Page
- 148 - 157
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International Standard Serial Number (ISSN)
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