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Inflammasome functional activities in B lymphocytes

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Abstract

Studies in animal models and human subjects have shown that, in addition to their implication in innate immunity, inflammasomes also can play a role in adaptive immunity. However, the contribution of the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway to adaptive immunity remains incompletely explored. Here, we show that NLRP3 plays an important role in different facets of B cell functions, including proliferation, antibody production, and secretion of inflammatory and anti-inflammatory cytokines. When exposed to B cell receptor engagement, Toll-like receptor activation, stimulation in conditions that mimic T cell-dependent responses, or NLRP3 activation, B cells manifest disparate responses and produce different cytokine patterns critical for modulating innate and adaptive immunity, indicating that the cytokines produced serve a critical link between the early innate immune response and the delayed adaptive immunity. Importantly, genetic ablation of nlrp3 reduced the inflammasome-mediated functions of B cells. We propose that, in the absence of other cell types, the potential of B lymphocytes to respond to NLRP3 engagement enables them to initiate inflammatory cascades through recruitment of other cell subsets, such as macrophages and neutrophils. Since NLRP3 activation of B cells is not followed by pyroptosis, even in the presence of a basal caspase-1 activity, this pathway acts as a bridge that optimizes interactions between the innate and adoptive branches of the immune response.

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Data availability

No datasets were generated or analyzed during the current study.

Abbreviations

ASC:

Sensory protein adaptor protein

CpG:

Unmethylated cytosine guanine oligonucleotide

DAMPs:

Damage-associated molecular patterns

GC:

Germinal center

Ig:

Immunoglobuin

NLRP3:

Nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3

PAMPs:

Pathogen-associated molecular patterns

PHB:

Prohibitin (PHB)

PRRs:

Pattern recognition receptors (PRRs)

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Funding

MZ is supported by the China Medical University (Taichung, Taiwan) and by a Senior Jade Mountain Award (Ministry of Education, Taipei, Taiwan).

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Authors and Affiliations

  1. Graduate Institute of Biomedical Sciences, China Medical University, No. 91號, Xueshi Road, North District, 404, Taichung, Taiwan

    Man Lun Hsu, Kai Fu Jhuang & Moncef Zouali

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  1. Man Lun Hsu
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  2. Kai Fu Jhuang
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  3. Moncef Zouali
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Contributions

MLH performed the experiments and participated in drafting the paper; KFJ performed experiments; MZ designed, supervised the experiments, and wrote the paper.

Corresponding author

Correspondence to Moncef Zouali.

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This study was approved by the review board from China Medical University, Taichung (Taiwan).

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Hsu, M.L., Jhuang, K.F. & Zouali, M. Inflammasome functional activities in B lymphocytes. Immunol Res 72, 828–840 (2024). https://doi.org/10.1007/s12026-024-09490-9

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