Research article summary (published 27 Feb 2007):

Anti-nuclear antibody production and autoimmunity in transgenic mice that overexpress the transcription factor Bright.

Full Abstract

The B cell-restricted transcription factor, B cell regulator of Ig(H) transcription (Bright), up-regulates Ig H chain transcription 3- to 7-fold in activated B cells in vitro. Bright function is dependent upon both active Bruton's tyrosine kinase and its substrate, the transcription factor, TFII-I. In mouse and human B lymphocytes, Bright transcription is down-regulated in mature B cells, and its expression is tightly regulated during B cell differentiation. To determine how Bright expression affects B cell development, transgenic mice were generated that express Bright constitutively in all B lineage cells. These mice exhibited increases in total B220(+) B lymphocyte lineage cells in the bone marrow, but the relative percentages of the individual subpopulations were not altered. Splenic immature transitional B cells were significantly expanded both in total cell numbers and as increased percentages of cells relative to other B cell subpopulations. Serum Ig levels, particularly IgG isotypes, were increased slightly in the Bright-transgenic mice compared with littermate controls. However, immunization studies suggest that responses to all foreign Ags were not increased globally. Moreover, 4-wk-old Bright-transgenic mice produced anti-nuclear Abs. Older animals developed Ab deposits in the kidney glomeruli, but did not succumb to further autoimmune sequelae. These data indicate that enhanced Bright expression results in failure to maintain B cell tolerance and suggest a previously unappreciated role for Bright regulation in immature B cells. Bright is the first B cell-restricted transcription factor demonstrated to induce autoimmunity. Therefore, the Bright transgenics provide a novel model system for future analyses of B cell autoreactivity.

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Author information

Author/s: Shankar, Malini (M); Nixon, Jamee C (JC); Maier, Shannon (S); Workman, Jennifer (J); Farris, A Darise (AD); Webb, Carol F (CF);

Affiliation: Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, 825 NE 13th Street, Oklahoma City, OK 73104, USA.

Grants: AI 044215 (Agency:United States NIAID)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol), published in United States. (Language: eng)

Reference: 2007-Mar; vol 178 (issue 5) : pp 2996-3006

Dates: Created 2007/02/21; Completed 2007/04/24; Revised 2007/11/15;

PMID: 17312145, status: MEDLINE (last retrieval date: 11/6/2008)

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.

Animals Antibodies, Antinuclear - biosynthesis; immunology Antibody Formation - genetics; immunology Antigens, CD45 - immunology Autoimmune Diseases - blood; genetics; immunology; pathology Autoimmunity - genetics; immunology B-Lymphocytes - immunology; pathology DNA-Binding Proteins - biosynthesis; genetics; immunology Down-Regulation - genetics; immunology

Down-Regulation - genetics; immunology Gene Expression Glomerulonephritis - blood; genetics; immunology; pathology Humans Immunoglobulin G - blood; immunology Mice Mice, Transgenic Oncogenes - genetics; immunology Trans-Activators - biosynthesis; genetics; immunology

Associated Chemicals: Antibodies, Antinuclear (0) ; Arid3a protein, mouse (0) ; DNA-Binding Proteins (0) ; Immunoglobulin G (0) ; Trans-Activators (0) ; Antigens, CD45 (EC 3.1.3.48)

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