Objective To study the role of B lymphocytes in systemic sclerosis (SSc). Methods Peripheral B cell subpopulations and the production of interleukin‐6 (IL‐6) and transforming growth factor β (TGFβ) were analyzed using flow cytometry and multiplex assay. The fibroblast proliferation rate upon incubation with supernatants from B cells isolated from SSc patients or healthy controls was assessed using XTT, bromodeoxyuridine, and Ki‐67. Collagen production was assessed using a collagen assay. Results Ninety untreated patients (12 males) fulfilling the American College of Rheumatology/European League Against Rheumatism criteria for SSc (23 with diffuse cutaneous SSc dcSSc and 67 with limited cutaneous SSc lcSSc) and 30 healthy controls were recruited. Increased proportions of B cells expressing CD69 and CD95 were identified among the patients with SSc. B lymphocytes from dcSSc patients versus lcSSc patients and healthy controls expressed increased proportion of cells positive for CD5 (mean ± SD 24.12 ± 7.93% versus 14.09 ± 6.58% P = 0.03 and 14.21 ± 5.34% P = 0.01), CD86 (39.89 ± 22.11% versus 17.72 ± 13.98% P = 0.0007 and 11.68 ± 11.09% P < 0.001), IL‐6 receptor (IL‐6R; 33.64 ± 23.12% versus 17.91 ± 13.62% P < 0.0001 and 12.08 ± 8.68% P = 0.0009), or IL‐21R (32.55 ± 20.19% versus 5.76 ± 4.40% P < 0.0001 and 5.93 ± 3.29% P < 0.0001). In addition, the levels of IL‐6 (mean ± SD 314.3 ± 317.8 pg/ml versus 6.10 ± 2.58 pg/ml; P = 0.0007) and TGFβ (mean ± SD 1,020 ± 569 pg/ml versus 163.8 ± 98.69 pg/ml; P = 0.001) secreted by B lymphocytes from patients with SSc were increased compared to healthy controls. Fibroblast proliferation and collagen production were also significantly increased in the presence of B cell supernatant from SSc patients as compared to healthy controls. Conclusion The numbers of activated B cells were increased in SSc patients, and the up‐regulation of CD5, CD86, IL‐6R, and IL‐21R discriminated between patients with dcSSc and those with lcSSc. Peripheral B lymphocytes from SSc patients secreted both IL‐6 and TGFβ, and they activated fibroblasts in vitro.