Differential Expression of IgM and IgD Discriminates Two Subpopulations of Human Circulating IgM+IgD+CD27+ B Cells That Differ Phenotypically, Functionally, and Genetically

Bautista, Diana; Vásquez, Camilo; Ayala-Ramírez, Paola; Téllez-Sosa, Juan; Godoy-Lozano, Elizabeth Ernestina; Martínez-Barnetche, Jesús; Franco, Manuel; Ángel, Juana

doi:10.3389/fimmu.2020.00736

Cited by 35 publications

(38 citation statements)

References 75 publications

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“…However, prior to this, it will be beneficial to utilize exploratory approaches, such as single-cell RNAseq, to characterize these MZB-like cells residing within non-splenic tissue compartments of humans. Ongoing studies within the field would allow for direct comparison and quantification of transcriptomic similarities of these RM-residing B cells to traditional splenic MZB, as well as circulating MZB and other B cell subsets 34 . This will provide critical foundational information as to the natural function of these cells within the RM, as well as providing insight into how these cells could potentially participate in propagating HIV replication.…”

Section: Discussionmentioning

confidence: 99%

Ex vivo rectal explant model reveals potential opposing roles of Natural Killer cells and Marginal Zone-like B cells in HIV-1 infection

Smith

Murray

Amancha

et al. 2020

Sci Rep

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Our understanding of innate immune responses in human rectal mucosal tissues (RM) and their contributions to promoting or restricting HIV transmission is limited. We defined the RM composition of innate and innate-like cell subsets, including plasmacytoid dendritic cells; CD1c + myeloid DCs; neutrophils; macrophages; natural killer cells (NK); Marginal Zone-like B cells (MZB); γδ T cells; and mucosal-associated invariant T cells in RM from 69 HIV-negative men by flow cytometry. Associations between these cell subsets and HIV-1 replication in ex vivo RM explant challenge experiments revealed an inverse correlation between RM-NK and p24 production, in contrast to a positive association between RM-MZB and HIV replication. Comparison of RM and blood-derived MZB and NK illustrated qualitative and quantitative differences between tissue compartments. Additionally, 22 soluble molecules were measured in a subset of explant cultures (n = 26). Higher production of IL-17A, IFN-γ, IL-10, IP-10, GM-CSF, sFasL, Granzyme A, Granzyme B, Granulysin, and Perforin following infection positively correlated with HIV replication. These data show novel associations between MZB and NK cells and p24 production in RM and underscore the importance of inflammatory cytokines in mucosal HIV infection, demonstrating the likely critical role these innate immune responses play in early mucosal HIV replication in humans.

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Section: Discussionmentioning

confidence: 99%

Ex vivo rectal explant model reveals potential opposing roles of Natural Killer cells and Marginal Zone-like B cells in HIV-1 infection

Smith

Murray

Amancha

et al. 2020

Sci Rep

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“…The relevance of reduced TNF production by MZ‐like B cells after phototherapy requires further investigation. MZ‐like B cells represent a population of B cells that respond primarily to microbial signatures via TLRs and can undergo immunoglobulin class switching when activated with cytokines and TLR ligands 26 . In particular, MZ‐like B cells may be activated by neutrophils and undergo class switching in response to interferon‐γ 27 .…”

Section: Discussionmentioning

confidence: 99%

Narrowband UVB phototherapy reduces TNF production by B‐cell subsets stimulated via TLR7 from individuals with early multiple sclerosis

et al. 2020

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Objectives. At the end of a 60-day course of narrowband UVB phototherapy, administered to individuals with early multiple sclerosis, there were changes in the relative proportions of circulating B-cell subsets. This study investigated phototherapyassociated changes to cytokine responses of B cells when exposed to a TLR7 ligand. Methods. PBMCs from participants of the PhoCIS (Phototherapy for Clinically Isolated Syndrome) trial taken before (day 1) and after phototherapy for 8 weeks (day 60) were incubated with, or without, the TLR7 ligand, R848, for 18 h. Production of TNF and IL-10 in seven B-cell subsets was examined, with cytokine responses in each individual at day 60, adjusted for responses at day 1. Paired PBMCs were from participants administered phototherapy (n = 7) or controls (n = 6). Results. At day 60, significantly fewer B cells, particularly marginal zone-like B cells (CD27 + /IgD +), from participants administered phototherapy produced TNF in response to TLR7 stimulation. When responses by seven B-cell subsets were analysed together using multivariate methods, a phototherapy-specific signature was observed. An increased responsiveness from day 1 to day 60 in IgM-only memory B cells (CD27 + /IgD À /IgM +) after TLR7 stimulation also predicted slower progression from CIS to MS. Phototherapy was without significant effect on B-cell IL-10 production. Conclusions. Reduced TNF responses after TLR7 stimulation in marginal zonelike B cells from participants administered phototherapy suggested treatment-associated priming effects that were detected upon subsequent polyclonal B-cell activation. Changes in responsiveness to TLR7 stimulation also suggested that IgM-only memory B cells may be important in conversion from CIS to MS.

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“…Plasmablasts (PB) and antibody-secreting cell (ASC)-like cells were excluded from analyses, as shown in Figures 1 and 2 , respectively. MZ-like B cells (CD27 + IgD + IgM + ) were divided into IgM hi and IgM lo MZ-like B cells as recently described ( 7 ). CD32b expression on all B cell subsets was examined using MFI.…”

Section: Methodsmentioning

confidence: 99%

“…MBC are often defined as CD27 + B cells, but these are in fact a heterogeneous population that include marginal zone (MZ)-like B cells (IgM + IgD + ), IgM-only MBC (IgM + IgD − ), and class switched MBC (IgD − /IgG +/− /IgA +/− /IgE +/− ). Each may exhibit diverse functional activities, in part due to differential expression of molecules such as CD21 and T bet ( 7 – 9 ), independent of their B cell receptor (BCR) isotype. Moreover, CD27 − B cells can also be antigen experienced, including IgD − CD27 − cells, the so-called double negative (DN) B cells, which may be IgM + or IgM - ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

et al. 2021

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B cells are critical to the development of multiple sclerosis (MS), but the mechanisms by which they contribute to the disease are poorly defined. We hypothesised that the expression of CD32b (FcγRIIb), a receptor for the Fc region of IgG with inhibitory activities in B cells, is lower on B cell subsets from people with clinically isolated syndrome (CIS) or MS. CD32b expression was highest on post-naive IgM+ B cell subsets in healthy controls. For females with MS or CIS, significantly lower CD32b expression was identified on IgM+ B cell subsets, including naive and IgMhi MZ-like B cells, when compared with control females. Lower CD32b expression on these B cell subsets was associated with detectable anti-Epstein Barr Virus viral capsid antigen IgM antibodies, and higher serum levels of B cell activating factor. To investigate the effects of lower CD32b expression, B cells were polyclonally activated in the presence of IgG immune complexes, with or without a CD32b blocking antibody, and the expression of TNF and IL-10 in B cell subsets was assessed. The reduction of TNF but not IL-10 expression in controls mediated by IgG immune complexes was reversed by CD32b blockade in naive and IgMhi MZ-like B cells only. However, no consequence of lower CD32b expression on these cells from females with CIS or MS was detected. Our findings highlight a potential role for naive and marginal zone-like B cells in the immunopathogenesis of MS in females, which requires further investigation.

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Differential Expression of IgM and IgD Discriminates Two Subpopulations of Human Circulating IgM+IgD+CD27+ B Cells That Differ Phenotypically, Functionally, and Genetically

Cited by 35 publications

References 75 publications

Ex vivo rectal explant model reveals potential opposing roles of Natural Killer cells and Marginal Zone-like B cells in HIV-1 infection

Ex vivo rectal explant model reveals potential opposing roles of Natural Killer cells and Marginal Zone-like B cells in HIV-1 infection

Narrowband UVB phototherapy reduces TNF production by B‐cell subsets stimulated via TLR7 from individuals with early multiple sclerosis

FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis

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