Research Article
Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus
Andreas Hutloff, Kerstin Büchner, Karin Reiter, Hans J. Baelde,
Marcus Odendahl, Annett Jacobi, Thomas Dörner,
Richard A. Kroczek,
Hans J. Baelde
Leiden University Medical Center, Leiden, The Netherlands
Search for more papers by this authorThomas Dörner
University Hospital Charité, Berlin, Germany
Drs. Dörner and Kroczek contributed equally to this work.
Search for more papers by this authorCorresponding Author
Richard A. Kroczek
Robert Koch Institute, Berlin, Germany
Drs. Dörner and Kroczek contributed equally to this work.
Molecular Immunology, Robert Koch Institute, Nordufer 20, D-13353 Berlin, GermanySearch for more papers by this authorAndreas Hutloff, Kerstin Büchner, Karin Reiter, Hans J. Baelde,
Marcus Odendahl, Annett Jacobi, Thomas Dörner,
Richard A. Kroczek,
Hans J. Baelde
Leiden University Medical Center, Leiden, The Netherlands
Search for more papers by this authorThomas Dörner
University Hospital Charité, Berlin, Germany
Drs. Dörner and Kroczek contributed equally to this work.
Search for more papers by this authorCorresponding Author
Richard A. Kroczek
Robert Koch Institute, Berlin, Germany
Drs. Dörner and Kroczek contributed equally to this work.
Molecular Immunology, Robert Koch Institute, Nordufer 20, D-13353 Berlin, GermanySearch for more papers by this authorAbstract
Objective
In systemic lupus erythematosus (SLE), the increased generation of memory B cells and plasma cells leads to autoimmune hypergammaglobulinemia and destructive immunoglobulin deposits in the kidneys. We undertook this study to determine the biologic mechanism driving this overactivation of the B cell compartment, which is the central issue in SLE.
Methods
We used flow cytometry to analyze expression of the T cell–specific inducible costimulator (ICOS) and its ligand (ICOS-L) on B cells obtained from the peripheral blood of SLE patients. We correlated ICOS-L expression with the differentiation status of the B cells using a large panel of surface antigens. In addition, SLE kidneys were analyzed by immunohistology.
Results
We found an increased expression of ICOS on CD4+ as well as CD8+ T cells in SLE. At the same time, we documented a down-regulation of ICOS-L on a high proportion of peripheral blood memory B cells. Based on in vitro experiments, we inferred that this ICOS-L down-regulation on B cells was a signature of recent interaction with ICOS+ T cells in vivo. In the kidneys of SLE patients, we found clusters of B cells and plasma cells in close contact with ICOS+ T cells.
Conclusion
Detailed analysis of B cells with down-regulated ICOS-L suggests that ICOS is one of the forces driving the formation of memory B cells and plasma cells in SLE. Furthermore, our identification of plasma cells in areas of T cell–B cell interaction in kidneys suggests that components of a T cell–driven B cell activation process may take place in peripheral tissues in SLE.
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