Impaired clearance of apoptotic cells in germinal centers: Implications for loss of B cell tolerance and induction of autoimmunity

Research output: Contribution to journalReview article

20 Citations (Scopus)

Abstract

Germinal centers (GCs) comprise lymphoid microenvironments where antigen-stimulated B cells undergo rapid proliferation and somatic hypermutation (SHM), resulting in the generation of B cells with high affinity for antigen. However, this process also generates B cell clones with low antigen affinity and with the potential for autoreactivity. It has been suggested that GC B cells with low antigen affinity and autoreactivity are eliminated via apoptosis and are rapidly cleared by tingible body macrophages (TBMus). Inefficient clearance of apoptotic cells (ACs) results in autoimmunity that is thought to be mediated by various intracellular molecules possessing danger-associated molecular patterns (DAMPs), including nuclear self-Ags. DAMPs can be released from ACs undergoing "secondary necrosis" due to a disruption in AC clearance within GCs. This review discusses the role and mechanisms associated with impaired clearance of ACs in GCs in loss of B cell tolerance leading to autoantibody production and the development of autoimmunity.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalImmunologic Research
Volume51
Issue number2-3
DOIs
StatePublished - Dec 1 2011

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Germinal Center
Autoimmunity
B-Lymphocytes
Antigens
Autoantibodies
Necrosis
Clone Cells
Macrophages
Apoptosis

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

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abstract = "Germinal centers (GCs) comprise lymphoid microenvironments where antigen-stimulated B cells undergo rapid proliferation and somatic hypermutation (SHM), resulting in the generation of B cells with high affinity for antigen. However, this process also generates B cell clones with low antigen affinity and with the potential for autoreactivity. It has been suggested that GC B cells with low antigen affinity and autoreactivity are eliminated via apoptosis and are rapidly cleared by tingible body macrophages (TBMus). Inefficient clearance of apoptotic cells (ACs) results in autoimmunity that is thought to be mediated by various intracellular molecules possessing danger-associated molecular patterns (DAMPs), including nuclear self-Ags. DAMPs can be released from ACs undergoing {"}secondary necrosis{"} due to a disruption in AC clearance within GCs. This review discusses the role and mechanisms associated with impaired clearance of ACs in GCs in loss of B cell tolerance leading to autoantibody production and the development of autoimmunity.",
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Impaired clearance of apoptotic cells in germinal centers : Implications for loss of B cell tolerance and induction of autoimmunity. / Rahman, Ziaur.

In: Immunologic Research, Vol. 51, No. 2-3, 01.12.2011, p. 125-133.

Research output: Contribution to journalReview article

TY - JOUR

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T2 - Implications for loss of B cell tolerance and induction of autoimmunity

AU - Rahman, Ziaur

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AB - Germinal centers (GCs) comprise lymphoid microenvironments where antigen-stimulated B cells undergo rapid proliferation and somatic hypermutation (SHM), resulting in the generation of B cells with high affinity for antigen. However, this process also generates B cell clones with low antigen affinity and with the potential for autoreactivity. It has been suggested that GC B cells with low antigen affinity and autoreactivity are eliminated via apoptosis and are rapidly cleared by tingible body macrophages (TBMus). Inefficient clearance of apoptotic cells (ACs) results in autoimmunity that is thought to be mediated by various intracellular molecules possessing danger-associated molecular patterns (DAMPs), including nuclear self-Ags. DAMPs can be released from ACs undergoing "secondary necrosis" due to a disruption in AC clearance within GCs. This review discusses the role and mechanisms associated with impaired clearance of ACs in GCs in loss of B cell tolerance leading to autoantibody production and the development of autoimmunity.

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