NKB cells: A double-edged sword against inflammatory diseases

Abstract

Interferon-γ (IFN-γ)-producing natural killer (NK) cells and innate lymphoid cells (ILCs) activate the adaptive system’s B and T cells in response to pathogenic invasion; however, how these cells are activated during infections is not yet fully understood. In recent years, a new lymphocyte population referred to as “natural killer-like B (NKB) cells”, expressing the characteristic markers of innate NK cells and adaptive B cells, has been identified in both the spleen and mesenteric lymph nodes during infectious and inflammatory pathologies. NKB cells produce IL-18 and IL-12 cytokines during the early phases of microbial infection, differentiating them from conventional NK and B cells. Emerging evidence indicates that NKB cells play key roles in clearing microbial infections. In addition, NKB cells contribute to inflammatory responses during infectious and inflammatory diseases. Hence, the role of NKB cells in disease pathogenesis merits further study. An in-depth understanding of the phenotypic, effector, and functional properties of NKB cells may pave the way for the development of improved vaccines and therapeutics for infectious and inflammatory diseases.

Natural killer-like B cells are a distinct but infrequent innate immune cell subset modulated by SIV infection of rhesus macaques

“…Many studies have observed NKB cells to be enriched within various tissues, including the spleen and mucosae [ 1 , 3 , 9 ]. To rule out the potential nonspecific binding of antibodies, mononuclear cells from RM spleen were stained and analyzed by ImageStream cytometry.…”

“…The rationale for choosing this method over more commonly used droplet-based methods (e.g. 10X Genomics) was three-fold: (i) the vastly improved signal in Smart-Seq allows for a high level of confidence to determine if a transcript is expressed or absent on a ‘per cell’ basis, and this resolution is not possible with droplet-based technology due to its inherently high drop-out level [ 3 ]; (ii) the rarity of NKB cells necessitates a high efficiency recovery method; and (iii) this approach allows for sequencing across the full-length of the transcript.…”

“…Recently, NKB cells have gained recognized importance as first responder cells that initiate and activate the innate and adaptive immunity in inflammation and infections and have been proposed for therapeutic interventions [ 3 ]. NKB cells express both B and NK cell receptors, but they have been described to be distinct from both NK and B cell subsets.…”

“…Outside of our group, NKB cells have been identified within the colon of SIV-infected RM and cynomolgus macaques as a lymphocyte subset which has the properties and functions of NK and B cells while remaining a distinct cell population [ 2 , 9 ]. Indeed, NKB cells have been identified as functionally relevant to the occurrence of inflammation within the colon of NHP via their increased proliferation and production of inflammatory cytokines such as interleukin-18 (IL-18) during SIV infection [ 2 , 3 ]. Furthermore, NKB cells have been shown to exist within human spleen and MLN, and have been observed to activate other innate lymphocytes via secretion of IL-18 and IL-12 to mediate the inflammatory response to microbial infection [ 4 , 9 ].…”

Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells

“…Interferon-γ (IFN-γ), also called immune interferon, is an important cytokine present in the tumor microenvironment (TME). IFN-γ is mainly induced by mitogens or cytokines (such as IL-12 and IL-18), and is expressed in immune cells, especially T cells and natural killer (NK) cells 1 , 2 . IFN-γ binds to its receptors on the cell membrane, including the two subunits IFNGR1 and IFNGR2, forming a receptor complex that in turn activates the downstream JAK-STAT1 signal transduction pathway 3 and performs a series of biological functions.…”