TY - JOUR
T1 - Impaired clearance of apoptotic cells in germinal centers
T2 - Implications for loss of B cell tolerance and induction of autoimmunity
AU - Rahman, Ziaur S.M.
N1 - Funding Information:
Acknowledgments We acknowledge the support of grants from the National Institute of Health (AR055701) and the National Arthritis Research Foundation (ANRF) to Z.S.M.R. I thank Drs. Tim Manser, Catherine Calkins, and Kerstin Kiefer for critical reading of the manuscript and comments.
PY - 2011/12
Y1 - 2011/12
N2 - 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.
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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U2 - 10.1007/s12026-011-8248-4
DO - 10.1007/s12026-011-8248-4
M3 - Review article
C2 - 22038528
AN - SCOPUS:84856537215
SN - 0257-277X
VL - 51
SP - 125
EP - 133
JO - Immunologic Research
JF - Immunologic Research
IS - 2-3
ER -