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PMID: 11970877 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The impact of T helper and T regulatory cells on the regulation of anti-double-stranded DNA B cells.

Immunity ·Vol. 16 ·No. 4 ·2002-04-00 ·Pages 535-46

Seo SJ, Fields ML, Buckler JL, Reed AJ, Mandik-Nayak L, Nish SA, Noelle RJ, Turka LA, Finkelman FD, Caton AJ, Erikson J

Abstract

Autoreactive B cells that appear to be inactivated can be found in healthy individuals. In this study, we examined the potential of these anergic cells to become activated. We show that anergy of anti-double-stranded DNA (dsDNA) B cells in BALB/c mice is readily reversed, requiring only the provision of T cell help. We further show that spontaneous loss of anergy among anti-dsDNA B cells in autoimmune lpr/lpr mice occurs in two phases: an abortive initial response to T help followed by full loss of tolerance. Strikingly, the abortive response can be reproduced in nonautoimmune mice when CD4+CD25+ T regulatory cells are administered in conjunction with CD4+ T helper cells, suggesting that loss of B cell tolerance may require both the production of T cell help and the overcoming of T suppression.

MeSH Terms

Abatacept Animals Antigens, CD Antigens, Differentiation/immunology B-Lymphocytes/cytology,immunology B7-1 Antigen/immunology CD28 Antigens/immunology CD4-Positive T-Lymphocytes/immunology CD40 Antigens/immunology CD40 Ligand/immunology CTLA-4 Antigen Cell Differentiation Clonal Anergy/immunology DNA/immunology Female Immunoconjugates Lymphocyte Activation/immunology Male Mice Mice, Inbred BALB C Mice, Inbred MRL lpr Mice, Transgenic Models, Immunological Receptors, CXCR5 Receptors, Chemokine Receptors, Cytokine/biosynthesis,immunology Receptors, Interleukin-2/immunology Spleen/cytology,immunology T-Lymphocytes, Helper-Inducer/immunology

Chemicals

Antigens, CD Antigens, Differentiation B7-1 Antigen CD28 Antigens CD40 Antigens CTLA-4 Antigen CXCR5 protein, mouse Ctla4 protein, mouse Immunoconjugates Receptors, CXCR5 Receptors, Chemokine Receptors, Cytokine Receptors, Interleukin-2 CD40 Ligand Abatacept DNA

Authors & Affiliations

11 authors, click to expand affiliations / ORCID

Seo Su-jean

The Wistar Institute, Philadelphia, PA 19104, USA.

Fields Michele L

Buckler Jodi L

Reed Amy J

Mandik-Nayak Laura

Nish Simone A

Noelle Randolph J

Turka Laurence A

Finkelman Fred D

Caton Andrew J

Erikson Jan

Article Info

Journal

Immunity

Abbr.

Immunity

ISSN

1074-7613

DOI

10.1016/s1074-7613(02)00298-4

Published

2002-04-00

Pages

535-46

Language

English

Region

United States

NLM ID

9432918

Subset

Grants

NIAID NIH HHS · AI 24541 · United States

NIAID NIH HHS · AI 32137 · United States

NIAMS NIH HHS · AR 49713 · United States

External Links

PubMed source DOI: 10.1016/s1074-7613(02)00298-4 View journal details

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The impact of T helper and T regulatory cells on the regulation of anti-double-stranded DNA B cells.

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