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

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 2

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LN B cells in RF Tg infected mice compared with uninfected mice. B. burg...
LN B cells in RF Tg infected mice compared with uninfected mice. B. burgdorferi infection is associated with B cell activation and IgM production. Intermediate-affinity RF B cells appear specially sensitive to activation. (A and B) Flow cytometry analysis of LN cells from infected and uninfected mice. Analysis was performed as in Figure 1A. Numbers indicate the mean percentage for 5–13 mice. Differences between percentages of cells from infected versus uninfected mice are statistically significant for all lines (P < 0.05, Mann-Whitney test). (C) Numbers of IgM+B220+ B cells in infected animals, determined by cytofluorimetry in pooled LNs, relative to uninfected controls. Each value ± 1 SD represents the mean ratio from 5–13 mice. (D) Lymphadenomegaly in infected animals. Shown are spleen and inguinal LNs from an infected Hul × cIgG mouse (bottom), compared with the uninfected control (top). (E) Surface expression of CD86 on gated RF B cells (IgMa+17.109+) and non-RF B cells (IgMa+17.109low/–) 30 days after B. burgdorferi infection (thick line) in the Hul × cIgG line. (F) Levels of serum IgM in infected mice compared with controls. IgM levels were measured by ELISA. Values represent the mean relative increase of the total IgM production from day 0 to day 30 in infected mice (black bars) and uninfected mice (white bars). *P < 0.05, Mann-Whitney test. Numbers of tested animals are those represented in Figure 3A. Bckgd, background.