The Journal of Immunology, 2008,
180,
2007
-2008
Copyright © 2008 by The American Association of Immunologists, Inc.
Comment on "Activation-Induced Cytidine Deaminase Expression in Follicular Dendritic Cell Networks and Interfollicular Large B Cells Supports Functionality of Ectopic Lymphoid Neogenesis in Autoimmune Sialoadenitis and MALT Lymphoma in Sjögren’s Syndrome"
Olivier Thaunat* and
Antonino Nicoletti
* Département de Transplantation et d’Immunologie Clinique Hôpital Edouard Herriot, Hospices Civils de Lyon Université Claude Bernard Lyon-I Institut National de la Santé et de la Recherche MédicaleS, Unité 851 Lyon, France
Centre de Recherche des Cordeliers Université Pierre et Marie Curie Université Paris Descartes Unité Mixte de Recherche S 872 Institut National de la Santé et de la Recherche Médicale, Unité 872, Paris, France
We read with interest the paper published by Bombardieri et al. (1) in the October 1, 2007 issue of The Journal of Immunology.
In line with what we have previously published on chronic allograft rejection (2), the authors report that activation-induced cytidine deaminase (AID) is expressed by B cells of ectopic germinal centers (tertiary lymphoid organs or TLOs) associated with autoimmune sialoadenitis. Because AID is the key enzyme triggering class switch recombination (CSR) and somatic hypermutation (SHM) (3), these results strongly support that a local selection and proliferation of reactive B cells take place within disease-targeted organs and these data therefore fit with the findings that pathogenic Abs are produced within chronically inflamed tissues (4, 5).
However, we would like to challenge the second statement made by the authors that the level of AID expression is directly correlated with the one of CD21L, an isoform of CR2 selectively expressed by follicular dendritic cells (FDCs). Indeed, while we observed such a correlation in "professional lymphoid tissue" (Fig. 1A), we did not find a statistically significant correlation when the analysis was performed on TLOs (Fig. 1B). Indeed, in these tissues the level of expression of CD21L was stable from one sample to another while AID levels were extremely variable. Because FDCs likely play the same role regardless of the nature of the Ag (auto VS allo), we conclude that, although necessary, FDCs are not sufficient to promote the activation of the CSR/SHM machinery in B cells during lymphoid neogenesis.
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FIGURE 1. The expressions of AID, CD21L, and GAPDH (used as endogenous control for normalization) were measured by quantitative PCR in "professional" secondary lymphoid organs (12 lymph nodes and five tonsils) and TLOs (38 consecutive, chronically rejected renal grafts). The relative expression of AID was plotted against the relative expression of CD21L. Linear regression showed a close correlation between AID and CD21L mRNA expression in "professional" secondary lymphoid organs (A). In contrast, these two parameters are not correlated in TLOs (B). Given that the level of expression of CD21L is not predictive of the ability of the TLOs to switch on AID expression, we conclude that FDCs are not sufficient to promote the activation of the CSR/SHM machinery in B cells during lymphoid neogenesis.
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References
- Bombardieri, M., F. Barone, F. Humby, S. Kelly, M. McGurk, P. Morgan, S. Challacombe, S. De Vita, G. Valesini, J. Spencer, C. Pitzalis. 2007. Activation-induced cytidine deaminase expression in follicular dendritic cell networks and interfollicular large B cells supports functionality of ectopic lymphoid neogenesis in autoimmune sialoadenitis and MALT lymphoma in Sjögren’s syndrome. J. Immunol. 179: 4929-4938. [Abstract/Free Full Text]
- Thaunat, O., N. Patey, E. Morelon, J. B. Michel, A. Nicoletti. 2006. Lymphoid neogenesis in chronic rejection: the murderer is in the house. Curr. Opin. Immunol. 18: 576-579. [Medline]
- Durandy, A.. 2003. Activation-induced cytidine deaminase: a dual role in class-switch recombination and somatic hypermutation. Eur. J. Immunol. 33: 2069-2073. [Medline]
- Salomonsson, S., M. V. Jonsson, K. Skarstein, K. A. Brokstad, P. Hjelmstrom, M. Wahren-Herlenius, R. Jonsson. 2003. Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjögren’s syndrome. Arthritis Rheum. 48: 3187-3201. [Medline]
- Thaunat, O., A. C. Field, J. Dai, L. Louedec, N. Patey, M. F. Bloch, C. Mandet, M. F. Belair, P. Bruneval, O. Meilhac, et al 2005. Lymphoid neogenesis in chronic rejection: evidence for a local humoral alloimmune response. Proc. Natl. Acad. Sci. USA 102: 14723-14728. [Abstract/Free Full Text]
