Mechanisms of B cell autoimmunity in SLE

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyperreactivity. The underlying causes of the diffuse B-cell over-reactivity are unclear, but potential candidates include (a) intrinsic hyper-reactivity leading to polyclonal B-...

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Main Authors:	Dörner, Thomas, Giesecke, Claudia, Lipsky, Peter E
Format:	Online
Language:	English
Published:	BioMed Central 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308063/

id	pubmed-3308063
recordtype	oai_dc
spelling	pubmed-33080632012-04-27 Mechanisms of B cell autoimmunity in SLE Dörner, Thomas Giesecke, Claudia Lipsky, Peter E Review Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyperreactivity. The underlying causes of the diffuse B-cell over-reactivity are unclear, but potential candidates include (a) intrinsic hyper-reactivity leading to polyclonal B-cell activation with disturbed activation thresholds and ineffective negative selection; (b) lack of immunoregulatory functions; (c) secondary effects of an overactive inflammatory environment, such as overactive germinal center and ectopic follicular activity; and/or (d) disturbed cytokine production by non-B immune cells. These mechanisms are not mutually exclusive and may operate to varying extents and at varying times in SLE. Phenotypic and molecular studies as well as the results of recent clinical trials have begun to provide new insights to address these possibilities. Of importance, new information has made it possible to distinguish between the contribution played by abnormalities in central checkpoints that could lead to a pre-immune repertoire enriched in autoreactive B cells, on the one hand, and the possibility that autoimmunity arises in the periphery from somatic hypermutation and abnormal selection during T cell-dependent B-cell responses on the other. There is an intriguing possibility that apoptotic material bound to the surface of follicular dendritic cells positively selects autoreactive B cells that arise from non-autoreactive B-cell precursors as a result of somatic hypermutation and thereby promotes the peripheral emergence of autoimmunity. BioMed Central 2011 2011-10-27 /pmc/articles/PMC3308063/ /pubmed/22078750 http://dx.doi.org/10.1186/ar3433 Text en Copyright ©2011 BioMed Central Ltd
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Dörner, Thomas Giesecke, Claudia Lipsky, Peter E
spellingShingle	Dörner, Thomas Giesecke, Claudia Lipsky, Peter E Mechanisms of B cell autoimmunity in SLE
author_facet	Dörner, Thomas Giesecke, Claudia Lipsky, Peter E
author_sort	Dörner, Thomas
title	Mechanisms of B cell autoimmunity in SLE
title_short	Mechanisms of B cell autoimmunity in SLE
title_full	Mechanisms of B cell autoimmunity in SLE
title_fullStr	Mechanisms of B cell autoimmunity in SLE
title_full_unstemmed	Mechanisms of B cell autoimmunity in SLE
title_sort	mechanisms of b cell autoimmunity in sle
description	Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyperreactivity. The underlying causes of the diffuse B-cell over-reactivity are unclear, but potential candidates include (a) intrinsic hyper-reactivity leading to polyclonal B-cell activation with disturbed activation thresholds and ineffective negative selection; (b) lack of immunoregulatory functions; (c) secondary effects of an overactive inflammatory environment, such as overactive germinal center and ectopic follicular activity; and/or (d) disturbed cytokine production by non-B immune cells. These mechanisms are not mutually exclusive and may operate to varying extents and at varying times in SLE. Phenotypic and molecular studies as well as the results of recent clinical trials have begun to provide new insights to address these possibilities. Of importance, new information has made it possible to distinguish between the contribution played by abnormalities in central checkpoints that could lead to a pre-immune repertoire enriched in autoreactive B cells, on the one hand, and the possibility that autoimmunity arises in the periphery from somatic hypermutation and abnormal selection during T cell-dependent B-cell responses on the other. There is an intriguing possibility that apoptotic material bound to the surface of follicular dendritic cells positively selects autoreactive B cells that arise from non-autoreactive B-cell precursors as a result of somatic hypermutation and thereby promotes the peripheral emergence of autoimmunity.
publisher	BioMed Central
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308063/
_version_	1611515513391808512

Mechanisms of B cell autoimmunity in SLE

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