BackgroundCytokine‐producing B cells play a well‐established role in modifying immune responses in chronic inflammatory diseases. We characterized B‐cell cytokine responses against periodontitis‐associated bacteria in patients with periodontitis.MethodsBlood and saliva samples were collected from patients with periodontitis grade B (N = 31) or grade C (N = 25), and 25 healthy controls (HCs). Mononuclear cells were stimulated with Porphyromonas gingivalis, Fusobacterium nucleatum, Staphylococcus epidermidis, or Cutibacterium acnes, and B‐cell production of tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, interferon (IFN)‐γ, IL‐10 and transforming growth factor (TGF)‐β by B cells was assessed by flow cytometry.ResultsHCs had higher baseline frequencies of B cells producing IFN‐γ or TNF‐α than grade B patients, but only B cells from grade B patients showed significant differentiation into IFN‐γ‐, TNF‐α‐, TGF‐β‐, or IL‐10‐producing cells after challenge with P. gingivalis and into IFN‐γ‐, TGF‐β‐, or IL‐10‐producing cells after challenge F. nucleatum. Notably, the baseline frequency of IL‐10‐producing B cells from grade C patients correlated inversely with clinical attachment loss (AL). The major proportion of the IFN‐γ‐ and TGF‐β‐producing B cells were CD27+ memory cells, while the IL‐10‒producing B cells were mainly CD27−CD5−.ConclusionsB cells from grade B patients, particularly those harboring P. gingivalis, showed proinflammatory B‐cell responses to P. gingivalis. Moreover, the baseline frequency of IL‐10‐producing B cells in the grade C group correlated inversely with AL, suggesting a diminished immunoregulatory capacity of IL‐10‒producing B cells in these patients.