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The Journal of Immunology, 2008, 180, 2008 -2009
Copyright © 2008 by The American Association of Immunologists, Inc.
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Response to 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"

Michele Bombardieri, Francesca Barone and Costantino Pitzalis

Centre for Experimental Medicine and Rheumatology Sir John Vane Science Centre William Harvey Research Institute Barts and The London School of Medicine and Dentistry London, United Kingdom

We thank Thaunat and Nicoletti (1) for their interest in our paper on activation-induced cytidine deaminase (AID) expression in the salivary glands (SG) of patients with Sjögren’s syndrome (SS) (2) and for their comments.

Based on their data on ectopic lymphoid tissue formation in chronically rejected renal grafts, the authors suggest that the expression levels of CD21L mRNA, an isoform of CR2 exclusively expressed by follicular dendritic cells (FDCs), do not correlate with those of AID in ectopic lymphoid tissue.

Although we have no reason to doubt the above findings in chronically rejected renal grafts, we have clearly demonstrated that in the parotid glands of SS patients with lymphoepithelial sialoadenitis and MALT lymphoma there is a close association between AID and CD21L mRNA levels. In addition, the levels of both AID and CD21L mRNA in the SG analyzed were similar or even higher than those observed in normal lymph nodes, suggesting that the chronically inflamed parotid glands of some SS patients recapitulate features and functions of secondary lymphoid organs. In this regard, this observation is in keeping with what Thaunat and Nicoletti reported, i.e., the close association between AID and CD21L in human secondary lymphoid organs.

Contrary to what Thaunat and Nicoletti described for chronically rejected renal grafts in which CD21L mRNA levels appear to be homogenously expressed in different samples, we would like to point out that it is well known that the expression of CD21L mRNA in ectopic lymphoid tissues in the target organs of several chronic autoimmune diseases varies widely among different patients.

As an example, in rheumatoid arthritis CD21L mRNA has been detected by semiquantitative RT-PCR in ~25% of patients (3), and the levels of CD21L mRNA varied significantly even among positive synovial biopsies (4). We observed very similar results in the SS SG that we have analyzed. Overall, this suggests that one should take caution in directly comparing ectopic lymphoid tissue formation in rather different disease settings, as in chronic graft rejection and autoimmune diseases.

Nevertheless, we agree with Thaunat and Nicoletti that the exact relationship between FDC network formation and AID expression in ectopic lymphoid tissue is yet to be defined and requires further investigation.

References

  1. Thaunat, O., A. Nicoletti. 2008. 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". J. Immunol. 180: 2007-2008. [Free Full Text]
  2. 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]
  3. Takemura, S., A. Braun, C. Crowson, P. J. Kurtin, R. H. Cofield, W. M. O’Fallon, J. J. Goronzy, C. M. Weyand. 2001. Lymphoid neogenesis in rheumatoid synovitis. J. Immunol. 167: 1072-1080. [Abstract/Free Full Text]
  4. Timmer, T. C., B. Baltus, M. Vondenhoff, T. W. Huizinga, P. P. Tak, C. L. Verweij, R. E. Mebius, T. C. van der Pouw Kraan. 2007. Inflammation and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected by genomics technology: identification of the interleukin-7 signaling pathway in tissues with lymphoid neogenesis. Arthritis Rheum. 56: 2492-2502. [Medline]




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