Hu & Zhang Lab
The State Key Laboratory of Biotherapy Si-Chuan University

Neutrophils license iNKT cells to regulate self-reactive mouse B cell responses

The innate immune system is important not only for serving as the first line against infection, but also for initiating and regulating adaptive immunity. The immune response under inflammation is tightly regulated to prevent autoimmunity. A recent study uncovers a new mechanism of how innate immune cells restrict excessive B cell response. In this study, they reveal that under the condition of infection causing inflammasome activation, neutrophils facilitate innate-type invariant natural killer T cells (iNKT) to negatively regulate self-reactive B cell response. This study gives us a new insight into how neutrophils interact with iNKT cells to restrict autoimmunity and further studies may target on harnessing this interplay in therapeutic approaches to cure autoimmune disease.

The authors show that peritoneal injection of IL-18 triggers an interaction between neutrophils and iNKT cells that facilitates the activation of each other in spleen. Interestingly, activated neutrophlis upregulate their secretion of BAFF to support B cell survival, but they conversely facilitate iNKT cells to restrict autoreactive B cell response. Neutrophils license iNKT cells to adopt a cytotoxic phenotype mediated by FasL, which is of significance for the restriction of B cell response, as depletion of FasL would otherwise diminish this effect. The suppression of B cell response by iNKT cells is endowed by neutrophils. Depletion of neutrophils results in immoderate B cell response manifested by increased production of self-reactive antibodies, augmented germinal center formation and plasma cell response. Thus, neutrophils unexpectedly restrict autoreactive B cell response in this inflammasome-driven inflammatory environment.

ORIGINAL RESEARCH PAPER Thomas,H, et al. Neutrophils license iNKT cells to regulate self-reactive mouse B cell responses. Nature Immunology 17, 14071414 (2016)

By Yanli