B cell-intrinsic IFN-g promotes CD11c+ age-associated B cell differentiation and compromises affinity-based germinal center selection in lupus
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ABSTRACT:
PROVIDER: PRJNA1132944 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29734579_1.fastq.gz | Fastqsanger.gz | |||
| SRR29734579_2.fastq.gz | Fastqsanger.gz |
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Project description:Lupus patients respond less efficiently to vaccinations and are more susceptible to infections. Previously, we have shown, in lupus models, that excessive CD11c+ age-associated B cells (ABCs) not only contribute to autoantibody production but also compromise antigen-specific germinal center (GC) B cell selection and affinity maturation by promoting aberrant T cell activation. Yet, how CD11c+ ABC differentiation is regulated is not fully understood. Here we show that B cell-intrinsic IFN-γ is required for excessive CD11c+ ABC differentiation in lupus mice. B cell-intrinsic IFN-γ is mainly produced by CD11c+ ABCs. IFN-γ-deficiency leads to decreased expression of ABC characteristic genes, including Zeb2, an ABC-specific transcription factor recently described. We further show that ablating IFN-γ can normalize T cell overactivation and rescue antigen-specific GC responses in lupus mice. Our study offers insight into the crucial role of B cell-intrinsic IFN-γ in promoting CD11c+ ABC differentiation and compromising affinity-based germinal center selection and affinity maturation in lupus, providing a potential target for lupus treatment.
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