Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides

Rachel Brummel; Petar Lenert

doi:10.4049/jimmunol.174.4.2429

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Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides

Journal article

Open access

Peer reviewed

Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides

Rachel Brummel and Petar Lenert

The Journal of immunology (1950), Vol.174(4), pp.2429-2434

02/15/2005

DOI: 10.4049/jimmunol.174.4.2429

PMID: 15699180

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Abstract

Several types of CpG-oligodeoxynucleotides (ODN) have been recently characterized. In mice, type A(D) CpG-ODNs primarily stimulate macrophages and dendritic cells, but fail to stimulate B cells. On the contrary, type B(K) CpG-ODNs are excellent B cell activators. Type C CpG-ODNs combine features of both types A(D) and B(K) CpG-ODNs. Despite cell type preferences, all CpG-ODNs require the presence of TLR9 for activation. In this study, we show that a subset of B cells from lupus mice responds to type A(D) CpG-ODN stimulation vigorously and directly with increased CD25 and CD86 expression and IL-10 secretion. Furthermore, these CpG-ODNs induce high surface IgM expression and promote 50- to 100-fold higher IgM and IgG3 secretion in lupus B cells than in controls. This response is similar to that seen with bacterial DNA stimulation of B cells. Type A(D)-responsive cells are enriched within lupus B cells with the marginal zone (MZ) phenotype. These cells are at least twice more numerous in lupus mice than in controls. The ability of lupus B cells to respond to type A(D) CpG-ODN stimulation is not due to differential TLR9 expression. Therefore, type A(D) CpG-ODNs may contribute to the lupus pathogenesis by inducing MZ-B cell activation, costimulatory molecule expression, and polyclonal Ig secretion. Through increased IL-10 secretion, MZ-B cells may also modify the activity of other cell types, particularly dendritic cells and macrophages.

Adjuvants, Immunologic - pharmacology

Antigens, CD - biosynthesis

Membrane Glycoproteins - biosynthesis

Lupus Erythematosus, Systemic - metabolism

B7-2 Antigen

Lymphocyte Activation - immunology

Mice, Inbred MRL lpr

CD40 Antigens - metabolism

Immunoglobulin G - biosynthesis

Oligodeoxyribonucleotides - classification

Lupus Erythematosus, Systemic - immunology

Interleukin-10 - metabolism

B-Lymphocyte Subsets - immunology

Female

Mice, Inbred DBA

CpG Islands - immunology

Receptors, Interleukin-2 - biosynthesis

Mice, Inbred C57BL

Hypergammaglobulinemia - immunology

Mice, Inbred NZB

Animals

B-Lymphocyte Subsets - metabolism

Up-Regulation - immunology

Mice

Mice, Inbred BALB C

Oligodeoxyribonucleotides - pharmacology

Lupus Erythematosus, Systemic - pathology

Immunoglobulin M - biosynthesis

Details

Title: Subtitle: Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides
Creators: Rachel Brummel - Division of Rheumatology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Petar Lenert
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.174(4), pp.2429-2434
DOI: 10.4049/jimmunol.174.4.2429
PMID: 15699180
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: AI047374-01A2 / NIAID NIH HHS
Language: English
Date published: 02/15/2005
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094487002771

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