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Autoantigen, innate immunity, and T cells cooperate to break B cell tolerance during bacterial infection
Pauline Soulas, … , Thierry Martin, Anne-Sophie Korganow
Pauline Soulas, … , Thierry Martin, Anne-Sophie Korganow
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2257-2267. https://doi.org/10.1172/JCI24646.
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Research Article Immunology Article has an altmetric score of 3

Autoantigen, innate immunity, and T cells cooperate to break B cell tolerance during bacterial infection

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Abstract

Autoantibody production during infections is considered to result from nonspecific activation of low-affinity autoreactive B cells. Whether this can lead to autoimmune disease remains uncertain. We show that chronic infection by Borrelia burgdorferi of Tg animals expressing human rheumatoid factor (RF) B cells (of low or intermediate affinities) in the absence or in the constitutive presence of the autoantigen (represented here by chimeric IgG with human constant region) breaks their state of immunological ignorance, leading to the production of RFs. Surprisingly, this production was more pronounced in intermediate-affinity RF Tg mice coexpressing the autoantigen. This overproduction was mediated by immune complexes and involved synergistic signaling between the B cell receptor and Toll-like receptors and T cell help. These findings indicate that chronic infection can activate autoreactive B cells with significant affinity and creates conditions that can drive them to differentiate into memory cells. Such cells may have some physiological yet undetermined role, but in autoimmune-prone individuals, this scenario may initiate autoimmunity.

Authors

Pauline Soulas, Anne Woods, Benoit Jaulhac, Anne-Marie Knapp, Jean-Louis Pasquali, Thierry Martin, Anne-Sophie Korganow

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Figure 1

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B cells in Hul and Hul × cIgG mice. Hul × cIgG RF B cells develop normal...
B cells in Hul and Hul × cIgG mice. Hul × cIgG RF B cells develop normally and remain functionally ignorant. (A) Flow cytometry of splenocytes from Hul and Hul × cIgG mice. Viable lymphocytes are gated on forward scatter (FSC) and side scatter (SSC) parameters. B220 staining reflects total B cells; IgMa is the Tg heavy chain allotype; 17.109 is the Tg light chain idiotype. Numbers indicate the mean percentage in the quadrants or the outlined gates. (B) Percentages of follicular B cells assessed by CD21 and CD23 expression on splenic 17.109+ cells. (C) Effects of in vitro stimulations on Hul and Hul × cIgG splenic B cells. Splenocytes were cultured for 72 hours in the presence of aggregated huIgG (aghuIgG, 1 mg/ml), anti-mouse IgM (10 μg/ml), or medium alone (nonstimulated [ns] or dashed line). Histograms show divisions of CFSE-labeled 17.109high B cells or surface expression of the CD86 activation marker on these cells.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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