IFN-I promotes T-cell–independent immunity and RBC autoantibodies via modulation of B-1 cell subsets in murine SCD

Shan Su, Weili Bao, Yunfeng Liu, Patricia A. Shi, Deepa Manwani, Irina Murakhovskaya, Sally Campbell-Lee, Cheryl A. Lobo, Avital Mendelson, Xiuli An, Hui Zhong, Woelsung Yi, Karina Yazdanbakhsh

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The pathophysiology of sickle cell disease (SCD) is characterized by hemolytic anemia and vaso-occlusion, although its impact on the adaptive immune responses remains incompletely understood. To comprehensibly profile the humoral immune responses, we immunized SCD mice with T-cell–independent (TI) and T-cell–dependent (TD) antigens (Ags). Our study showed that SCD mice have significantly enhanced type 2 TI (TI-2) immune responses in a manner dependent on the level of type I interferons (IFN-I), while maintaining similar or decreased TD immune responses depending on the route of Ag administration. Consistent with the enhanced TI-2 immune responses in SCD mice, the frequencies of B-1b cells (B-1 cells in humans), a major cell type responding to TI-2 Ags, were significantly increased in both the peritoneal cavity and spleens of SCD mice and in the blood of patients with SCD. In support of expanded B-1 cells, elevated levels of anti–red blood cell (anti-RBC) autoantibodies were detected in both SCD mice and patients. Both the levels of TI-2 immune responses and anti-RBC autoantibodies were significantly reduced after IFN-I receptor (IFNAR) antibody blockades and in IFNAR1–deficient SCD mice. Moreover, the alterations of B-1 cell subsets were reversed in IFNAR1–deficient SCD mice, uncovering a critical role for IFN-I in the enhanced TI-2 immune responses and the increased production of anti-RBC autoantibodies by modulating the innate B-1 cell subsets in SCD. Overall, our study provides experimental evidence that the modulation of B-1 cells and IFN-I can regulate TI immune responses and the levels of anti-RBC autoantibodies in SCD.

Original languageEnglish (US)
Pages (from-to)334-347
Number of pages14
JournalBlood
Volume145
Issue number3
DOIs
StatePublished - Jan 16 2025

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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