Rheumatoid factors induce signaling from B cells, leading to Epstein-Barr virus and B-cell activation.
B-cell antigen receptor signaling is initiated upon binding of the antigen to membrane-bound immunoblobulin (Ig), and the anti-Ig antibody (Ab) mimics this signaling. In B cells latently infected with Epstein-Barr virus (EBV), the same signals induce virus activation. We examine here whether rheumatoid factors (RFs), autoantibodies directed against the Fc portion of IgG, induce EBV and B-cell activation. As a source of RFs, RF-producing lymphoblastoid cell line (LCL) clones were isolated from peripheral blood mononuclear cells (PBMC) and synovial cells from patients with rheumatoid arthritis (RA) by EBV transformation. Burkitt's lymphoma-derived Akata cells, which are highly responsive to EBV activation by anti-Ig Abs, were used for the assay of EBV activation. Akata cells expressed IgG3 as membrane-bound Ig. RFs from a synovium-derived LCL were directed to IgG3 and induced EBV activation in 16 to 18% of Akata cells, whereas RFs from another synovium-derived LCL were directed to IgG1 and did not induce EBV activation. Pretreatment of RFs with the purified Fc fragment of human IgG completely abolished EBV activation. Furthermore, B-cell activation was assessed by incorporation of [3H]thymidine. RFs from synovium-derived LCLs efficiently induced B-cell activation, and the addition of CD40 ligand had a synergistic effect. On the other hand, RFs from PBMC-derived LCLs were polyreactive, had a lower affinity to IgG, and did not induce EBV and B-cell activation. The present findings imply a possible role for RFs as EBV and B-cell activators.
Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-0815, Japan.
Lixin
L
Yang
Masayuki
M
Hakoda
Kazuya
K
Iwabuchi
Tsuyoshi
T
Takeda
Takao
T
Koike
Naoyuki
N
Kamatani
Kenzo
K
Takada
D001172:Arthritis, Rheumatoid / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D002051:Burkitt Lymphoma / Q000276:immunology / Q000821:virology; D045744:Cell Line, Tumor; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D012217:Rheumatoid Factor / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction; D014775:Virus Activation; D017735:Virus Latency
D011947:Receptors, Antigen, B-Cell; D012217:Rheumatoid Factor