Failure To Detect Functional Neutrophil B Helper Cells in the Human Spleen

Abstract

A novel role for human neutrophilic granulocytes was recently described, showing that these cells, upon entering the spleen, can be reprogrammed into a distinct B cell-helper neutrophil phenotype that is capable of eliciting B cell responses such as immunoglobulin secretion, class switch recombination and somatic hypermutation. Using similar protocols, we detected a homogeneous population of CD15highCD16high neutrophils in fresh human spleen samples, which did not differ in phenotype and function from blood neutrophils. No phenotypic characteristics of costimulatory nature were detected on splenic or circulating neutrophils, nor could we reproduce the immunoglobulin production of splenic B cells in the presence of splenic neutrophils, although B cell function and neutrophil activity were normal. Independent confirmation of a role for NBH cells is required.

Social networking of human neutrophils within the immune system

“…57 The concept that human neutrophils can function as B-cell helpers has emerged by the demonstration that freshly isolated splenic neutrophils induce a T cell-independent antibody response by MZ B cells, via BAFF, APRIL, and IL-21 release. 29 Intriguingly, B-cell helper functions by splenic neutrophils have not been reproduced by other groups, 58 likely due to differences in the protocol used to collect, store, and process the splenic tissue and/or in the purity/manipulation of the neutrophil or B-cell populations, as pointed out by the same authors. 58 Conversely, recent in vivo data confirm that splenic mouse neutrophils support preimmune immunoglobulin (Ig)G3 production, as well as postimmune IgM, IgG2b, IgG2c, and IgG3 responses to repetitive immunization with polysaccharides such as 2,4,6-trinitrophenyl-ficoll (A. Chorny and A. Cerutti, unpublished data, 2014).…”

“…29 Intriguingly, B-cell helper functions by splenic neutrophils have not been reproduced by other groups, 58 likely due to differences in the protocol used to collect, store, and process the splenic tissue and/or in the purity/manipulation of the neutrophil or B-cell populations, as pointed out by the same authors. 58 Conversely, recent in vivo data confirm that splenic mouse neutrophils support preimmune immunoglobulin (Ig)G3 production, as well as postimmune IgM, IgG2b, IgG2c, and IgG3 responses to repetitive immunization with polysaccharides such as 2,4,6-trinitrophenyl-ficoll (A. Chorny and A. Cerutti, unpublished data, 2014). Neutrophils have also been proposed to play a role in the pathogenesis of B-cell lymphomas, either through the production of APRIL 59 or, based on studies in mice, through NET release 60 (supplemental Table 2).…”

Functional capacities of human IgM memory B cells in early inflammatory responses and secondary germinal center reactions

“…Human MGZ B cells have been reported specifically to interact with neutrophils that reside in close vicinity to the MGZ and to show B cell-helper function and induce Ig gene diversification via secretion of tumor necrosis factor superfamily members 13 and 13B and interleukin 21 (31), although a recent study contradicts these findings (32). Neutrophils are recruited to epithelial cells in injured or infected tissue by secretion of early cytokines.…”

Red pulp macrophages in the human spleen are a distinct cell population with a unique expression of Fc-γ receptors

“…22 Written informed consent for organ donation was obtained according to national regulations regarding organ donation. Splenic tissue of the organ donor was obtained during transplantation surgery as part of the standard diagnostic procedure for HLA typing, and was transported in University of Wisconsin Fluid at 4°C.…”