Interestingly, patients treated with anti-TNF- (entanercept) that binds to both TNF and LT have disrupted peripheral lymphoid germinal centers and reduced synovial TLT neogenesis [74, 75]. is necessary for the priming of T cells. The donor cells expressing CD80/CD86 either by B cells or B cell depleted splenocytes were insufficient to activate autoreactive T cells vivo. Open in a separate window Figure 3 Decrease in T cell and antibody in SCIDCD80/86?/? recipient mice. (A) T cell proliferation was measured by 3H-thymine incorporation in PG activated spleen cell cultures, (B) cytokine levels in supernatants from PG activated spleen cells, (C) serum human PG-specific antibody response, (D) serum mouse PG-specific. Data represents the mean and SEM (n=7). Data represent the mean and SEM (n=7). * represents statistically significantly differents em p /em 0.05 from the control group (BWTTWT) SCID. KIAA1516 We Ecdysone have reported that a B cell-specific deficiency of CD80/CD86 does not affect the initiation of autoantibodies despite a reduction in T cell activation . To determine whether a reduction in autoantibodies contributes to a decrease in arthritis severity, serum antibodies specific for human and na?ve mouse PG were assessed. The IgG1 anti-human and anti-mouse PG antibodies were significantly reduced in immunized SCIDCD80/CD86?/? mice reconstituted with either WT or CD80/CD86?/? donor cells whereas only the IgG2a anti-mouse was significantly decreased in CD80/CD86?/? recipient mice (Figure 3 C & D). These data demonstrate that the decrease in T cell and antibody responses coincided with the reduction in arthritis in SCIDCD80/CD86?/? mice reconstituted with either WT or CD80/CD86?/? donor cells. Collectively, these data demonstrate that the CD80/86 expression by the recipient APCs is necessary for T and B cells activation and indicate that B cell expression of CD80/86 is not sufficient to overcome the lack of expression of CD80/86 by other APCs. These data suggest that B cells may be more effective at activating memory T cells than priming of na?ve T cells. B cells in RA synovium The synovial tissue of RA patients Ecdysone can be divided into those with diffuse lymphocyte aggregates, those with T and B cells aggregates, and those with highly developed germinal centers designated as tertiary lymphoid tissue (TLT) that contain follicular dendritic cells, and segregated T and B cell areas [64, 65]. The development of TLTs is not Ecdysone unique to RA, but has been described to occur in other Ecdysone inflammatory conditions and is associated with chronic activation of the immune system . Chemokines and cytokines, many of which are necessary for secondary lymphoid organ development, regulate TLT neogenesis, complexity and size. In synovium there is an increase in the local expression of lympotoxin (LT) , LT, Ecdysone CXCL13, CCL21, CCL20, and CXCL12 where TLTs are present in comparison to tissue that forms diffuse lymphoid aggregates [65, 67-70]. Accordingly, the expression level of CXCL13 and LT is highly predictive of the presence of TLT . However, the role of CXCL13 may be secondary to LT for TLT neogenesis, as ectopic lymphoid cluster development in CXCL13 transgenic mice is dependent on B cells expression of LT . In a model of chronic arthritis, the CXCL13 ligand, CXCR5, and the CCL20 and CCL19 ligand, CXCR7, are necessary for the development TLT . B cell expression of LT and LT is also important for the maintenance of B cell follicles . Interestingly, patients treated with anti-TNF- (entanercept) that binds to both TNF and LT have disrupted peripheral lymphoid germinal centers and reduced synovial TLT neogenesis [74, 75]. Fewer patients were responsive to anti-TNF therapy if they were positive for TLT, however, abrogation of TLT features following anti-TNF therapy was associated with a clinical response . B cells in germinal centers of secondary lymphoid tissues are capable of undergoing affinity maturation through somatic hypermutation and class-switch recombination of the Ig genes, and potentially differentiating into memory B cells and antibody-secreting plasma cells [76, 77]. B cells accumulating in the synovium display.
Interestingly, patients treated with anti-TNF- (entanercept) that binds to both TNF and LT have disrupted peripheral lymphoid germinal centers and reduced synovial TLT neogenesis [74, 75]