Document Detail


Soluble antigen can impede affinity maturation and the germinal center reaction but enhance extrafollicular immunoglobulin production.
MedLine Citation:
PMID:  7543516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The primary immune response to T cell-dependent Ags develops in two pathways. These comprise the extrafollicular pathway, in which foci of Ab-secreting cells develop, and the intrafollicular pathway that gives rise to germinal centers and affinity maturation. We have previously shown that de-aggregated (4-hydroxy-3-nitrophenyl) acetyl (NP) coupled to the protein carrier human serum albumin (HSA), (NP-HSA), injected 6 days after challenge immunization with aggregated NP-HSA, resulted in impaired development of NP-specific, higher-affinity cells. Studies presented here describe the cellular basis underlying this impairment of affinity maturation. Using multiparameter flow cytometry, we show that mice injected with soluble NP-HSA ("tolerant" mice) develop significantly fewer NP-binding IgG1+ B220+ cells of germinal center origin than do the control ("immune") mice. In addition, using immunohistology, we noted that the spleens of tolerant mice had a marked reduction in the number of germinal centers that contained lambda-bearing cells, these being characteristic of the NP response in C57BL/6 mice. Curiously, germinal centers in the spleens of tolerant mice had more than twice the volumes of those in the immune spleens. In contrast to its effect on the germinal center pathway, soluble Ag enhanced the extrafollicular pathway, reflected by the increased numbers of B cells secreting IgM and IgG1 Abs specific for NP, HSA, and undefined Ags. Thus, soluble NP-HSA given after challenge immunization can impede affinity maturation of NP-specific cells, but enhance the extrafollicular pathway. These results are discussed in the context of the known capacity of some persisting Ags, e.g., malaria parasites, to frustrate affinity maturation and memory cell generation.
Authors:
B Pulendran; K G Smith; G J Nossal
Related Documents :
15899926 - Co-infection with trypanosoma brucei brucei prevents experimental autoimmune encephalom...
21286796 - Chemical mediators of inflammation and resolution in post-operative abdominal aortic an...
19609626 - Immune suppression of human lymphoid tissues and cells in rotating suspension culture a...
2521356 - Antibody to the murine type 3 complement receptor inhibits t lymphocyte-dependent recru...
20026096 - Use of human bronchial epithelial cells (beas-2b) to study immunological markers result...
20712456 - Interleukin-28 and interleukin-29: novel regulators of skin biology.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  155     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-09-12     Completed Date:  1995-09-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1141-50     Citation Subset:  AIM; IM    
Affiliation:
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antibody Formation*
Antigens, CD45
Antigens, Surface / analysis
Cell Differentiation
Cell Division
Flow Cytometry
Humans
Immune Tolerance*
Immunization
Immunoglobulin G / analysis
Male
Mice
Mice, Inbred C57BL
Nitrophenols / immunology*
Phenylacetates
Receptors, Antigen, B-Cell / analysis
Serum Albumin / immunology*
Solubility
Specific Pathogen-Free Organisms
Spleen / immunology*
Grant Support
ID/Acronym/Agency:
AI 03958/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Surface; 0/Immunoglobulin G; 0/Nitrophenols; 0/Phenylacetates; 0/Receptors, Antigen, B-Cell; 0/Serum Albumin; 10463-20-4/4-hydroxy-5-nitrophenyl acetic acid; EC 3.1.3.48/Antigens, CD45

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


Previous Document:  Costimulation of human CD4+ T cells with LFA-3 and B7 induce distinct effects on AP-1 and NF-kappa B...
Next Document:  Ex vivo coating of islet cell allografts with murine CTLA4/Fc promotes graft tolerance.