Document Detail


CR2+ marginal zone B cell production of pathogenic natural antibodies is C3 independent.
MedLine Citation:
PMID:  21187447     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Intestinal ischemia-reperfusion (IR)-induced damage requires complement receptor 2 (CR2) for generation of the appropriate natural Ab repertoire. Pathogenic Abs recognize neoantigens on the ischemic tissue, activate complement, and induce intestinal damage. Because C3 cleavage products act as ligands for CR2, we hypothesized that CR2(hi) marginal zone B cells (MZBs) require C3 for generation of the pathogenic Abs. To explore the ability of splenic CR2(+) B cells to generate the damaging Ab repertoire, we adoptively transferred either MZBs or follicular B cells (FOBs) from C57BL/6 or Cr2(-/-) mice into Rag-1(-/-) mice. Adoptive transfer of wild type CR2(hi) MZBs but not CR2(lo) FOBs induced significant damage, C3 deposition, and inflammation in response to IR. In contrast, similarly treated Rag-1(-/-) mice reconstituted with either Cr2(-/-) MZB/B1 B cells (B1Bs) or FOBs lacked significant intestinal damage and displayed limited complement activation. To determine whether C3 cleavage products are critical in CR2-dependent Ab production, we evaluated the ability of the natural Ab repertoire of C3(-/-) mice to induce damage in response to IR. Infusion of C3(-/-) serum into Cr2(-/-) mice restored IR-induced tissue damage. Furthermore, Rag-1(-/-) mice sustained significant damage after infusion of Abs from C3(-/-) but not Cr2(-/-) mice. Finally, adoptive transfer of MZBs from C3(-/-) mice into Rag-1(-/-) mice resulted in significant tissue damage and inflammation. These data indicate that CR2 expression on MZBs is sufficient to induce the appropriate Abs required for IR-induced tissue damage and that C3 is not critical for generation of the pathogenic Abs.
Authors:
Keith M Woods; Michael R Pope; Sara M Hoffman; Sherry D Fleming
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-27
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-20     Completed Date:  2011-03-07     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1755-62     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer
Animals
Autoantibodies / biosynthesis*,  therapeutic use
B-Lymphocyte Subsets / immunology*,  pathology,  transplantation
Cells, Cultured
Complement C3 / deficiency,  physiology*
Homeodomain Proteins / genetics
Immunophenotyping
Intestinal Mucosa / blood supply,  immunology,  pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Complement 3d / biosynthesis,  deficiency,  physiology*
Reperfusion Injury / immunology,  pathology,  therapy
Spleen / immunology*,  metabolism,  pathology
Grant Support
ID/Acronym/Agency:
AI061691/AI/NIAID NIH HHS; P20 RR016475/RR/NCRR NIH HHS; P20 RR016475-09/RR/NCRR NIH HHS; P20 RR017686/RR/NCRR NIH HHS; P20 RR017686/RR/NCRR NIH HHS; P20 RR017686-09/RR/NCRR NIH HHS; R01 AI061691/AI/NIAID NIH HHS; R01 AI061691-04/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Complement C3; 0/Homeodomain Proteins; 0/Receptors, Complement 3d; 128559-51-3/RAG-1 protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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