Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by the development of class-switched antinuclear antibodies. Multiple lines of evidence link germinal centers (GCs) with the genesis of autoantibody (autoAb)–producing plasma cells in SLE, including extensive somatic hypermutation in autoreactive B cell clones and the development of spontaneous GCs in both mouse lupus models and in human patients with lupus (Wellmann et al., 2005; Aloisi and Pujol-Borrell, 2006; Vinuesa et al., 2009). Importantly, rather than being downstream targets of T cell activation signals, autoreactive B cells can directly initiate breaks in T cell tolerance and spontaneous GC formation in SLE, via antigen presentation to CD4+ T cells in the context of MHC II (Gile s et al., 2015; Jackson et al., 2016). In addition to cognate interactions between B cells and T follicular helper (TFH) cells, cytokine signals profoundly influence GC biology in autoimmunity. Although type 1 IFN signals are strongly associated with lupus disease activity, recent work has shown that dysregulated type 2 IFN (IFN-γ) signals function early in disease to promote autoimmune GC formation. In independent lupus models, B and T cell–intrinsic IFN-γ receptor (IFN-γR) activation promotes the generation of GC B cells and TFH cells, respectively; suggesting that IFN-γ is critical for the initiation of spontaneous, autoimmune GCs (Lee et al., 2012; Domeier et al., 2016; Jackson et al., 2016). Importantly, these observations model longitudinal studies in human SLE showing that increased serum IFN-γ correlates with development of lupus-specific autoAb years before disease diagnosis or the development of a type 1 IFN signature. Notably, elevated serum IL-6 is also observed concurrently or before first positive autoAb in preclinical SLE, suggesting a key role for IL-6 signals in initiating breaks in B and/or T cell tolerance (Lu et al., 2016; Munroe et al., 2016). IL-6 facilitates early TFH differentiation by transiently inducing expression of the TFH master transcription factor BCL-6 (Nurieva et al., 2009). Whether IL-6 is required for GC formation, however, remains controversial. For example, although early studies reported reduced GCs in IL-6–deficient mice after T–dependent antigen immunization (Kopf et al., 1998; Nurieva et al., 2008; Wu et al., 2009), antiviral GC responses were not affected by IL-6 deletion (Poholek et al., 2010; Eto et al., 2011; Karnowski et al., 2012). Rather, deletion of both IL-6 and IL-21 blocked the antiviral GC response, whereas GCs were preserved after deletion of either cytokine alone, suggesting redundant roles in TFH recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (Gcs) in systemic lupus erythematosus (SLE) and other disorders. the mechanisms whereby B cells facilitate loss of t cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes t follicular helper (tFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell–derived IL-6 is required to trigger autoimmune Gcs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell–derived IL-6 abrogates spontaneous Gc formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFn-γ, consistent with the critical roles for B cell–intrinsic IFn-γ receptor signals in driving autoimmune Gc formation. together, these findings identify a key mechanism whereby B cells drive …