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In autoimmune diseases, the breakdown of immune tolerance leads to the development of autoreactive immune responses targeting self-structures, and subsequent tissue and organ damage. Although the complex immunobiological mechanisms of autoimmune processes are still not fully clear, altered B cell function and autoantibody production seem to play a special role in the development of numerous autoimmune diseases. Understanding the process of B cell activation and autoantibody production is particularly important not only for early diagnosis, but also for development of novel effective treatments. Follicular T helper (TFH) cells are special CD4 + T cells mediating antigen-specific naive or memory B cell activation within the B cell follicles of secondary lymphoid organs. TFH cells are generated from peripheral naive CD4 T cells in the T cell zone of these lymphoid organs. The differentiation of TFH cells begins with their migration to the border of T cell zone and B cell follicles. This follicular homing process is directed by B cell lymphoma 6 protein (Bcl-6), by coordinating the downregulation of CCR7, a receptor for certain T zone chemokines, and the up-regulation of CXCR5, the receptor for CXCL13. CXCL13 is a chemokine ligand secreted by follicular stromal cells in B cell follicles, which attracts primed T cells to the follicle edge, where they interact with antigen-primed B cells and differentiate into TFH cells. Interplay of TFH and activated B cells is essential for the generation of extrafollicular short-lived plasma cells producing low-affinity antibodies, and for germinal centre (GC) responses as well. Within GCs, TFH cells promote the development of high-affinity memory B cells and long-lived plasma cells by providing survival signals to centrocytes, which have undergone somatic hypermutation. Regarding the critical role of TFH cells in B cell activation and antibody production, their failure to maintain self-tolerance and potential contribution to autoimmunity has drawn much attention. Lessons learned from animal models, mainly murine models of SLE, shed light on altered TFH profiles in autoimmune conditions. First, the significance of IL-21, now considered the hallmark cytokine of TFH cells, was recognized in autoimmunity. Ozaki et al. [1] demonstrated enhanced IL-21 production in BXSB-Yaa mice, a model exhibiting lupus-like disease. IL-21 blockade or IL-21 receptor deficiency in lupus-prone MRL-Fas mice resulted in diminished lupus-associated features, including IgG deposits in glomeruli, circulating dsDNA autoantibodies, total IgG1 and IgG2a production, lymphadenopathy and spontaneous GC formation [2, 3]. Further studies examining TFH cells directly showed an aberrantly expanded TFH population. Interestingly, when Wu et al. [4] investigated the effect of nasal anti-CD3 on TFH cells in NZB/WF1 mice, CD4/ICOS/CXCR5 TFH cells obtained from anti-CD3treated mice showed decreased IL-21 and IL-17 expression and induced less IgG, IgG1 or IgG2a anti-dsDNA antibody production in an in vitro co-culture with naive CD19 B cells. Recent observations in autoimmune animal models have further enriched our knowledge about the development and function of TFH cells. In an elegant study, Linterman et al. [5] investigated the deletion of Sap (Sh2d1a) and the loss of one Bcl-6 allele in Roquin (sanroque) mice. They found that deletion of one Bcl-6 allele diminished spontaneous GC formation and the lupus phenotype. Moreover, the deficiency of the Sap molecule caused a dramatic reduction in CD4/ CXCR5/PD-1 TFH cells, IL-21 production, renal pathology, formation of GC and autoantibodies. Moreover, adoptive transfer of sanroque TFH cells into wild-type recipients resulted in spontaneous GC formation, underscoring the direct role of TFH cells in the development of lupus-associated autoimmunity. Investigations of human autoimmune diseases also suggest that aberrant TFH cell development and function can drive autoimmunity. Simpson et al. were the first to demonstrate altered TFH proportions in SLE patients. By determining CD4CXCR5ICOS and CD4CXCR5 PD-1 TFH cells in peripheral blood, they observed an overrepresented population of CD4ICOS and CD4CXCR5ICOS TFH cells, which showed an association with the high autoantibody titre and the presence of glomerulonephritis [6]. Subsequently expansion of circulating TFH cells has been reported in patients with various autoimmune diseases, such as SS, RA, JDM and autoimmune thyroid disorders. In primary SS, our group demonstrated that the elevated circulating CD4/ CXCR5/ICOS/PD-1 TFH cell percentages are associated with the presence of systemic extraglandular manifestations and anti-SSA/SSB positivity. Patients with higher TFH cell proportions also had elevated serum levels of IL-12 and IL-21 [7]. Maehara et al. [8] investigated the selective localization of Th1, Th2, Th17, regulatory T and TFH cells in labial salivary gland biopsies. They found that the expression of TFH and Th2-related molecules in infiltrating lymphocytes with ectopic GCs was higher than in those without ectopic GCs. An elevated percentage of circulating TFH cells was found in SLE. High TFH cell