How bacteria break B cell tolerance

July 23, 2005

(I-Newswire) - How bacteria break B cell tolerance

There is a lot of indirect evidence that microbial infections can

initiate and/or worsen autoimmune disease. Autoantibody production

during infection results from activation of low-affinity autoreactive B

cells. But how this could lead to autoimmune disease is not clear.

In a study appearing online on July 21 in advance of print publication

of the August 1 issue of the Journal of Clinical Investigation, Thierry

and colleagues from INSERM show in vivo that an experimental

infectious disease creates the necessary and sufficient conditions to

activate self-reactive B cells with significant affinity. This could

drive them to mature into harmful memory B cells and lead to autoimmune

diseases in susceptible individuals.

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.

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