Open AccessInvolvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus
Author(s) -
Hutloff Andreas,
Büchner Kerstin,
Reiter Karin,
Baelde Hans J.,
Odendahl Marcus,
Jacobi Annett,
Dörner Thomas,
Kroczek Richard A.
Publication year - 2004
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.20519
Subject(s) - immunology , cd8 , b cell , systemic lupus erythematosus , flow cytometry , plasma cell , cd40 , naive b cell , t cell , antibody , antigen , medicine , in vitro , immune system , biology , cytotoxic t cell , antigen presenting cell , pathology , disease , biochemistry
Abstract 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.