Natural history of MZ B cells

Nemazee, David

doi:10.1084/jem.20202700

Cited by 11 publications

(8 citation statements)

References 19 publications

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“… 27 Later, B cell defects may predispose to problematic secondary bacterial infection. 12 MZ B cells are key players in early defence against blood-borne bacterial infection, 28 and MZL cells are profoundly reduced in COVID-19, and hypoxia almost ablates MZ B cells in mice. This may also predispose to re-infection by new variants, as affinity maturation might generate a broader spectrum of neutralizing antibodies and B cell memory.…”

Section: Discussionmentioning

confidence: 99%

The impact of hypoxia on B cells in COVID-19

et al. 2022

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Section: Discussionmentioning

confidence: 99%

The impact of hypoxia on B cells in COVID-19

et al. 2022

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“…Human sMZ B cells combine features of innate and adaptive immune cells (1,17). These cells provide protection from lifethreatening infections with encapsulated bacteria, thought to be mainly derived from the protective function of IgM (4).…”

Section: Discussionmentioning

confidence: 99%

The Splenic Marginal Zone in Children Is Characterized by a Subpopulation of CD27-Negative, Lowly IGHV-Mutated B Cells

et al. 2022

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Young children and older adults suffer from enhanced susceptibility to infections with blood-borne pathogens. An essential step towards immunity is the establishment of a splenic marginal zone (sMZ), which is immature at below 2 years of age. At approximately 5 years of age, an adult level of protection is reached but wanes again in older adults. Although the infant sMZ is thought to contain mostly naïve B cells, memory B cells are recruited to and recirculate from the sMZ throughout life, and class-switched sMZ B cells dominate in older adults. For a better resolution of naïve versus memory B-cell subset accumulation in the sMZ, we performed a single cell-based gene expression analysis of (CD21highIgMhigh) sMZ B cells among five healthy donors (age 3 to 48 years) and validated the sMZ B-cell subset composition by flow cytometry of 147 spleen biopsies (age 0 to 82 years). We identified a major sMZ B-cell subpopulation, which is abundant at birth but decreases with age. These cells lack CD27 expression but carry a weak-to-intermediate memory B-cell signature. These CD27neg sMZ B cells are either IGHV-unmutated or carry only a few IGHV mutations early in life but show average memory B-cell IGHV mutation frequencies (>3%) in adults. The activation and proliferation potential of CD27neg sMZ B cells is significantly above that of non-sMZ B cells already in children. Our study suggests that the human sMZ B-cell pool changes with age, encompassing a major population of lowly Ig-mutated CD27neg but antigen-experienced B cells early in life.

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“…Later in the disease course B cell defects may predispose to secondary bacterial infection, which is a major clinical problem in severe COVID (Maes et al, 2021;Ripa et al, 2021). Marginal zone B cells are key players in early defence against blood--borne bacterial infection (Nemazee, 2021) and their dysregulation may play a role in autoimmunity (Tull et al, 2021). MZL B cells are profoundly reduced in COVID--19 in humans, and hypoxia results in MZs almost devoid of B cells in mice.…”

Section: Discussionmentioning

confidence: 99%

The impact of hypoxia on B cells in COVID-19

Kotagiri

Mescia

Hanson

et al. 2021

Preprint

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Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This brought to mind the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19. We demonstrated the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes we also observed in B cell VHL-deficient mice. This was corroborated by hypoxia-related transcriptional changes in COVID-19 patients, and by similar B cell abnormalities in mice kept in hypoxic conditions, including reduced marginal zone and germinal center B cells. Thus hypoxia might contribute to B cell pathology in COVID-19, and in other hypoxic states. Through this mechanism it may impact on COVID-19 outcome, and be remediable through early oxygen therapy.

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Natural history of MZ B cells

Cited by 11 publications

References 19 publications

The impact of hypoxia on B cells in COVID-19

The impact of hypoxia on B cells in COVID-19

The Splenic Marginal Zone in Children Is Characterized by a Subpopulation of CD27-Negative, Lowly IGHV-Mutated B Cells

The impact of hypoxia on B cells in COVID-19

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