Presence of Natural Killer B Cells in Simian Immunodeficiency Virus-Infected Colon That Have Properties and Functions Similar to Those of Natural Killer Cells and B Cells but Are a Distinct Cell Population

Cogswell, Andrew; Jo, Sungro; Ferguson, Natasha; Gupta, Kajal; Barker, Edward

doi:10.1128/jvi.00235-22

Cited by 3 publications

(19 citation statements)

References 76 publications

(119 reference statements)

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“…The signature pro-inflammatory cytokine IL-18 is produced by NKB cells together with IFN-g and TNF-a. The production of granzyme B and perforin confirmed the cytotoxic nature of NKB cells (27). Moreover, significantly increased production of granzyme A was found in NKB cells, compared with NK and CD8 + T cells.…”

Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...supporting

confidence: 60%

“…The role of NKB cells in gut-associated inflammation during mucosal immune responses to SIV infection was investigated ( 27 ). NKB cells present in the lamina propria of SIV-infected rhesus or cynomolgus macaque colons were compared with uninfected controls.…”

Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...mentioning

confidence: 99%

“…NKB cells present in the lamina propria of SIV-infected rhesus or cynomolgus macaque colons were compared with uninfected controls. RNA sequencing and flow-cytometry analyses showed that the NKB cells display receptors, markers, and functions similar to NK and B cells ( 27 ). The NKB cells were the primary source of IL-18 production in the colon following SIV infection.…”

Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...mentioning

confidence: 99%

“…Since IL-18 and IL-1β are canonically produced in response to inflammasome activation, IL-1β was investigated. IL-1β was produced by NK and B cells; however, no production was observed by the NKB cells ( 27 ). Thus, the NKB cells were concluded to be the primary source of IL-18, whose expression is highly regulated by a non-canonical pathway that mounts inflammatory responses in the SIV-infected colon.…”

Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...mentioning

confidence: 99%

“…In NK cells, the Fas ligand (FasL) targets and destroys virus-infected cells. An increased expression for FasL in NKB cells was observed during viral infection ( 27 ). Furthermore, over 84% of the NKB cells expressed FasL, compared with 10% and 14% of NK and CD8 + T cells, respectively.…”

Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...mentioning

confidence: 99%

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NKB cells: A double-edged sword against inflammatory diseases

Tandel

Negi²,

Tyagi³

2022

Front. Immunol.

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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.

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Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...supporting

confidence: 60%

Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...mentioning

confidence: 99%

Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...mentioning

confidence: 99%

Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...mentioning

confidence: 99%

Section: Nkb Cells and Their Role In Infectious And Inflammatory Dise...mentioning

confidence: 99%

See 3 more Smart Citations

NKB cells: A double-edged sword against inflammatory diseases

Tandel

Negi²,

Tyagi³

2022

Front. Immunol.

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

Manickam,

Upadhyay,

Woolley

et al. 2024

PLoS Pathog

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Natural killer-like B (NKB) cells are unique innate immune cells expressing both natural killer (NK) and B cell receptors. As first responders to infection, they secrete IL-18 to induce a critical cascade of innate and adaptive immune cell infiltration and activation. However, limited research exists on the role of NKB cells in homeostasis and infection, largely due to incomplete and erroneous evaluations. To fill this knowledge gap, we investigated the expression of signaling and trafficking proteins, and the in situ localization and transcriptome of naïve NKB cells comparied to conventionally-defined NK and B cells, as well as modulations of these cells in SIV infection. Intracellular signaling proteins and trafficking markers were expressed differentially on naïve NKB cells, with high expression of CD62L and Syk, and low expression of CD69, α4β7, FcRg, Zap70, and CD3z, findings which were more similar to B cells than NK cells. CD20+NKG2a/c+ NKB cells were identified in spleen, mesenteric lymph nodes (MLN), colon, jejunum, and liver of naïve rhesus macaques (RM) via tissue imaging, with NKB cell counts concentrated in spleen and MLN. For the first time, single cell RNA sequencing (scRNAseq), including BCR sequencing, of sorted NKB cells confirmed that NKB cells are unique. Transcriptomic analysis of naïve splenic NKB cells by scRNAseq showed that NKB cells undergo somatic hypermutation and express Ig receptors, similar to B cells. While only 15% of sorted NKB cells showed transcript expression of both KLRC1 (NKG2A) and MS4A1 (CD20) genes, only 5% of cells expressed KLRC1, MS4A1, and IgH/IgL transcripts. We observed expanded NKB frequencies in RM gut and buccal mucosa as early as 14 and 35 days post-SIV infection, respectively. Further, mucosal and peripheral NKB cells were associated with colorectal cytokine mileu and oral microbiome changes, respectively. Our studies indicate that NKB cells gated on CD3-CD14-CD20+NKG2A/C+ cells were inclusive of transcriptomically conventional B and NK cells in addition to true NKB cells, confounding accurate phenotyping and frequency recordings that could only be resolved using genomic techniques. Although NKB cells were clearly elevated during SIV infection and associated with inflammatory changes during infection, further interrogation is necessary to acurately identify the true phenotype and significance of NKB cells in infection and inflammation.

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Noncanonical B Cells: Characteristics of Uncharacteristic B Cells

Haas

2023

The Journal of Immunology

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B lymphocytes were originally described as a cell type uniquely capable of secreting Abs. The importance of T cell help in Ab production was revealed soon afterward. Following these seminal findings, investigators made great strides in delineating steps in the conventional pathway that B cells follow to produce high-affinity Abs. These studies revealed generalized, or canonical, features of B cells that include their developmental origin and paths to maturation, activation, and differentiation into Ab-producing and memory cells. However, along the way, examples of nonconventional B cell populations with unique origins, age-dependent development, tissue localization, and effector functions have been revealed. In this brief review, features of B-1a, B-1b, marginal zone, regulatory, killer, NK-like, age-associated, and atypical B cells are discussed. Emerging work on these noncanonical B cells and functions, along with the study of their significance for human health and disease, represents an exciting frontier in B cell biology.

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Presence of Natural Killer B Cells in Simian Immunodeficiency Virus-Infected Colon That Have Properties and Functions Similar to Those of Natural Killer Cells and B Cells but Are a Distinct Cell Population

Cited by 3 publications

References 76 publications

NKB cells: A double-edged sword against inflammatory diseases

NKB cells: A double-edged sword against inflammatory diseases

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

Noncanonical B Cells: Characteristics of Uncharacteristic B Cells

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