Mannose-binding lectin-deficient mice display defective apoptotic cell clearance but no autoimmune phenotype.
Mannose-binding lectin (MBL) is a circulating serum protein that is sequestered to sites of inflammation and infection. MBL is a member of the collectin family with structural similarities to the lung collectins and functional similarities to C1q. Both MBL and C1q activate complement; C1q activates the classical pathway and MBL the lectin pathway. Here we demonstrate that MBL binds apoptotic cells in vitro and confirm a role for MBL in clearance of apoptotic cells in vivo. Despite MBL null mice demonstrating defective apoptotic cell clearance they did not develop spontaneous autoimmunity, lymphoproliferation, or germinal center expansion although increased numbers of peritoneal B1 cells were detected. These data demonstrate an important in vivo role for MBL in clearance of dying cells and adds the MBL null animals to the few animals with demonstrable in vivo apoptotic cell clearance defects. Moreover, it demonstrates that failure of apoptotic cell clearance can be dissociated from autoimmunity.
Stuart
Lynda M
LM
Laboratory of Developmental Immunology, Harvard Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA. lstuart@partners.org
Takahashi
Kazue
K
Shi
Lei
L
Savill
John
J
Ezekowitz
R Alan B
RA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype
D000974:Antibodies, Antinuclear; D037601:Mannose-Binding Lectin