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. 2012:2012:789164.
doi: 10.1155/2012/789164. Epub 2012 Jun 4.

IgG4-Related Fibrotic Diseases from an Immunological Perspective: Regulators out of Control?

Laura C Lighaam  1 , Rob C Aalberse, Theo Rispens
Affiliations

IgG4-Related Fibrotic Diseases from an Immunological Perspective: Regulators out of Control?

Laura C Lighaam et al. Int J Rheumatol. 2012.

Abstract

Patients with autoimmune pancreatitis have a striking polyclonal elevation of total IgG4 in serum. This observation has been confirmed and extended to other fibrotic conditions (that are therefore called IgG4-related disease) but as yet remains unexplained. The affected tissue contains many IgG4-producing plasma cells embedded in a fibrotic matrix originating from activated mesenchymal (stellate) cells. We propose that the process results from an unusual interaction between two regulatory systems: the regulatory arm of the immune system (including Bregs) and the tissue repair regulatory components orchestrated by the activated stellate cell. This interaction results in ongoing mutual activation, generating TGFbeta, IL10, and vitamin D. This environment suppresses most immune reactions but stimulates the development of IgG4-producing plasma cells.

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Figures

Figure 1
Figure 1
Proposed model of B-cell infiltration into affected tissue. (a) B cells from the circulation enter the inflamed tissue. (b) Differential glycosylation of IgG4-switched B cells allows retention and activation of this cell type via an as-yet-unidentified lectin on the stellate cell. (c) In this model, the local environment of the affected tissue will further promote survival/proliferation of IgG4-switched B cells due to a tolerogenic environment that may in part be created via signals from the IgG4 B cells themselves.
Box 1
Box 1
IgG4-related disease (IRD).
Box 2
Box 2
The role of the myofibroblast-type stellate cell in fibrosis, tissue repair and plasma cell differentiation.
Box 3
Box 3
A quantitative conundrum: the number of tissue-residing plasma cells is insufficient to explain the strongly elevated IgG4 level in plasma.
See this image and copyright information in PMC

References

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