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Laboratoire d’Immunopathologie, Institut d’Hématologie et d’Immunologie, Strasbourg, France
It is well established that autoreactive B cells undergo negative
selection. This stands in paradox with the high frequency of so-called
natural autoreactive B cells producing low affinity polyreactive
autoantibodies with recurrent specificities, suggesting that these B
cells are selected on the basis of their autoreactivity. We previously
described two transgenic mouse lines (with and without IgD) producing a
human natural autoantibody (nAAb) that binds ssDNA and human Fc
. In
the absence of human IgG, nAAb-transgenic B cells develop normally. By
crossing these mice with animals expressing knockin chimeric IgG with
the human Fc, we now show that the constitutive expression of
chimeric IgG promotes the increase of nAAb-expressing B cells. This
positive selection is critically dependent on the presence of IgD,
occurs in the spleen, and concerns all mature B cell subsets, with a
relative preferential enrichment of marginal zone B cells. These data
support the view that soluble self-Ags can result in positive clonal
selection.
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