Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a fine balance

Noviski, Mark; Zikherman, Julie

doi:10.1016/j.coi.2018.09.015

Cited by 20 publications

(23 citation statements)

References 69 publications

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“…Recently, it has been shown that secreted IgM regulates B cell development by acting as a decoy for self-antigen [ 47 ]. It also seems that surface expression of IgM plays an important role in the direction of B cell subset differentiation [ 38 , 52 ]; mice lacking secreted IgM displaying increased BCR signaling developed increased MZ and decreased FO B cell numbers [ 47 , 53 ]. In atherosclerosis, loss of secreted IgM results in accelerated lesion formation due to reduced levels of B cells expressing the low-affinity IgE receptor CD23 and elevated IgE synthesis [ 54 ].…”

Section: Bcr Signaling B Cell Development and Atherosclerosismentioning

confidence: 99%

Functional Role of B Cells in Atherosclerosis

Shelby

Mußbacher

Galkina

2021

Cells

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Atherosclerosis is a lipid-driven inflammatory disease of blood vessels, and both innate and adaptive immune responses are involved in its development. The impact of B cells on atherosclerosis has been demonstrated in numerous studies and B cells have been found in close proximity to atherosclerotic plaques in humans and mice. B cells exert both atheroprotective and pro-atherogenic functions, which have been associated with their B cell subset attribution. While B1 cells and marginal zone B cells are considered to protect against atherosclerosis, follicular B cells and innate response activator B cells have been shown to promote atherosclerosis. In this review, we shed light on the role of B cells from a different, functional perspective and focus on the three major B cell functions: antibody production, antigen presentation/T cell interaction, and the release of cytokines. All of these functions have the potential to affect atherosclerosis by multiple ways and are dependent on the cellular milieu and the activation status of the B cell. Moreover, we discuss B cell receptor signaling and the mechanism of B cell activation under atherosclerosis-prone conditions. By summarizing current knowledge of B cells in and beyond atherosclerosis, we are pointing out open questions and enabling new perspectives.

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Section: Bcr Signaling B Cell Development and Atherosclerosismentioning

confidence: 99%

Functional Role of B Cells in Atherosclerosis

Shelby

Mußbacher

Galkina

2021

Cells

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“…Worth noting in biological systems function and homoeostasis depend on ne balance of molecules i.e. not necessarily the quantity [31,32]. However, using proteomic platform the identi ed PPs were selected based on quantity not function.…”

Section: Discussionmentioning

confidence: 99%

Sex-Biased Expression of Genes Allocated in the Autosomal Chromosomes: Lc-ms/ms Protein Profiling in Healthy Subjects

Giha¹,

Abdulwahab²,

Abbas³

et al. 2021

Preprint

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Sex and gender has large impact in human health and disease prediction. Men differ from women by a limited number of genes in Y chromosome while their phenotypes differ markedly. In this study, serum samples from healthy Bahraini men and women were analyzed by LC-MS/MS. Bioinformatics databases were used for proteins/peptides (PPs) identification and their gene localization. Results revealed that, the PPs which differed significantly (p<0.05 ANOVA) in abundance with fold change (FC) of ³1.5, were twenty, 11 were up-regulated in women (up to 8-folds), and 9 were up-regulated in men but with much lower FC, however, all PPs are encoded by genes located in autosomal chromosomes, indicative of sex-biased gene expression. The only PP related to sex, the sex hormone-binding globulin, was up-regulated in women. The remaining PPs were involved in immunity (6), lipid metabolism (5), gene expression (3) connective tissue (3), and others. The identified PPs were discussed within their physiological and pathological context, in relation to sex e.g. Apo-B100 (pathological cholesterol) was unregulated in men while the inflammatory/immunity related PPs, including Alpha-1-acid glycoproteins, were up-regulated in women. Finally, we propose proteomic as an ideal complementary tool for study of the molecular basis of the sex-biased gene expression.

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“…[ 30,43 ] The unique structure of the IgD‐class BCR that mediates ignorance to monovalent antigen [ 42 ] and a nano‐cluster‐specific surface expression whilst pairing with distinct coreceptors [ 71,72 ] suggests a specialized role in B cell biology. [ 44,73,74 ]…”

Section: The Role Of the Igd‐class Bcr In Adaptive Tolerancementioning

confidence: 99%

Adaptive tolerance: Protection through self‐recognition

Amendt

Jumaa

2022

BioEssays

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The random nature of immunoglobulin gene segment rearrangement inevitably leads to the generation of self‐reactive B cells. Avoidance of destructive autoimmune reactions is necessary in order to maintain physiological homeostasis. However, current central and peripheral tolerance concepts fail to explain the massive number of autoantibody‐borne autoimmune diseases. Moreover, recent studies have shown that in physiological mouse models autoreactive B cells were neither clonally deleted nor kept in an anergic state, but were instead able to mount autoantibody responses. We propose that activation of autoreactive B cells is induced by polyvalent autoantigen complexes that can occur under physiological conditions. Repeated encounter of autoantigen complexes leads to the production of affinity‐matured autoreactive IgM that protects its respective self‐targets from degradation. We refer to this novel mechanism as adaptive tolerance. This article discusses the discovery of adaptive tolerance and the unexpected role of high affinity IgM autoantibodies.

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Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a fine balance

Cited by 20 publications

References 69 publications

Functional Role of B Cells in Atherosclerosis

Functional Role of B Cells in Atherosclerosis

Sex-Biased Expression of Genes Allocated in the Autosomal Chromosomes: Lc-ms/ms Protein Profiling in Healthy Subjects

Adaptive tolerance: Protection through self‐recognition

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