Follicular exclusion of autoreactive B cells requires FcgammaRIIb.

Full Abstract

In non-autoimmune mice, the 3H9 transgenic Ig heavy chain can pair with endogenous Iglambda1 light chains to generate B cells with specificity for DNA. These autoreactive cells are actively regulated in vivo, as indicated by the exclusion of lambda1 cells from the splenic B cell follicle and the absence of auto-antibody production. To study the role of Fcgamma receptor IIb (FcgammaRIIb) in peripheral B cell tolerance, FcgammaRIIb(-/-) mice were crossed with C57BL/6 mice bearing a site-directed knock-in of the 3H9 transgene. 3H9FcgammaRIIb(-/-) mice become autoreactive, lose the follicular exclusion of anti-DNA B cells and instead have lambda1 B cells located within splenic germinal centers. They have increased frequencies of splenic auto-antibody-producing cells and elevated titers of IgG anti-DNA auto-antibody. The data implicate an FcgammaRIIb-dependent checkpoint that can exclude autoreactive B cells from splenic follicles. By restricting their participation in germinal center reactions, this putative checkpoint helps attenuate the production of potentially pathogenic auto-antibodies. The data further suggest that this FcgammaRIIb-dependent regulation is B cell autonomous.

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Author information

Author/s: Paul, Elahna (E); Nelde, Annette (A); Verschoor, Admar (A); Carroll, Michael C (MC);

Affiliation: Department of Pediatrics, Harvard Medical School, Boston, MA, USA. epaul(-atsign-)partners.org

Grants: P01AI52343 (Agency:NIAID NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: International immunology (Int Immunol), published in England. (Language: eng)

Reference: 2007-Apr; vol 19 (issue 4) : pp 365-73

Dates: Created 2007/03/30; Completed 2007/08/27; Revised 2007/12/03;

PMID: 17307801, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Age Factors
Animals
Antibodies, Antinuclear - analysis; blood; genetics; immunology
Antibodies, Antiphospholipid - analysis; genetics; immunology
Autoimmunity - immunology
B-Lymphocytes - immunology; metabolism
Bone Marrow Transplantation - immunology
Female
Germinal Center - cytology; immunology
Homeodomain Proteins - analysis; genetics
Immunoglobulin D - analysis
Immunoglobulin M - analysis
Immunoglobulin lambda-Chains - analysis

Immunoglobulin lambda-Chains - analysis
Immunophenotyping
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
Mice, Transgenic
Receptors, Complement 3d - analysis
Receptors, IgE - analysis
Receptors, IgG - genetics; immunology
Self Tolerance - immunology
Spleen - cytology; immunology
Syndecan-1 - analysis

Associated Chemicals: 3H9 protein, mouse (0) ; Antibodies, Antinuclear (0) ; Antibodies, Antiphospholipid (0) ; Fcgr2b protein, mouse (0) ; Homeodomain Proteins (0) ; Immunoglobulin D (0) ; Immunoglobulin M (0) ; Immunoglobulin lambda-Chains (0) ; Receptors, Complement 3d (0) ; Receptors, IgE (0) ; Receptors, IgG (0) ; Sdc1 protein, mouse (0) ; Syndecan-1 (0) ; RAG-1 protein (128559-51-3)

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