Impaired clearance of apoptotic cells induces the activation of autoreactive anti-Sm marginal zone and B-1 B cells.
Since apoptotic cell Ags are thought to be a source of self-Ag in systemic lupus erythematosus, we have examined the role of apoptotic cells in the regulation and activation of B cells specific for Sm, a ribonucleoprotein targeted in human and murine lupus. Using Ig-transgenic mice that have a high frequency of anti-Sm B cells, we find that apoptotic cell injection induces a transient splenic B cell response, while simultaneously causing extensive splenic and peritoneal anti-Sm B cell death. In contrast, mice deficient in the clearance of apoptotic cells develop a chronic anti-Sm response beginning at 1-2 mo of age. These mice have expanded marginal zone and B-1 B cell populations and anti-Sm B cells of both types are activated to form Ab-secreting cells. This activation appears to be Ag-specific, suggesting that activation is due to increased availability of apoptotic cell Ags. Since marginal zone and B-1 cells are positively selected, these data suggest a loss of ignorance rather than a loss of tolerance.
Qian
Ye
Y
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599.
Wang
Hongsheng
H
Clarke
Stephen H
SH
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010537:Peritoneum / Q000166:cytology / Q000276:immunology / Q000473:pathology; D010713:Phosphatidylcholines / Q000276:immunology; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D000076202:c-Mer Tyrosine Kinase; D055517:snRNP Core Proteins
D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D010713:Phosphatidylcholines; D011518:Proto-Oncogene Proteins; D017411:Ribonucleoproteins, Small Nuclear; C526416:Snrpb protein, mouse; D055517:snRNP Core Proteins; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase