Inflammasome functional activities in B lymphocytes

• Published in: Immunologic research Vol. 72; no. 4; pp. 828 - 840
• Main Authors: Hsu, Man Lun, Jhuang, Kai Fu, Zouali, Moncef
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2024; Springer Nature B.V
• Subjects: Adaptive Immunity; Allergology; Animal models; Animals; antibody formation; B-lymphocytes; B-Lymphocytes - immunology; Biomedical and Life Sciences; Biomedicine; Caspase-1; Cell activation; Cells, Cultured; Cytokines; Cytokines - metabolism; Humans; Immunity, Innate; Immunology; Inflammasomes; Inflammasomes - immunology; Inflammasomes - metabolism; Inflammation; Innate immunity; Internal Medicine; Leukocytes (neutrophilic); Lymphocyte Activation - immunology; Lymphocytes B; Lymphocytes T; Macrophages; Medicine/Public Health; Mice; Mice, Inbred C57BL; Mice, Knockout; neutrophils; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Oligomerization; Pyrin protein; Pyroptosis; Receptor mechanisms; secretion; Toll-like receptors; B cell; NLRP3; Innate immunity; Inflammasome; Adaptive immunity
• ISSN: 0257-277X; 1559-0755; 1559-0755
• DOI: 10.1007/s12026-024-09490-9

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.