Anti-tumour necrosis factor-α antibodies and B cell homeostasis in human inflammatory bowel diseases

BACKGROUND: The expression of CD70 on T cells is greatly enhanced by antigen-presenting cell (APC)-associated signals, such as tumour necrosis factor(TNF)-\u3b1, which is constitutionally high in patients with inflammatory bowel disease (IBD). Experimentally, the chronic activation of CD27 as a result of the constitutive expression of CD70 leads to the demise of B cells in bone marrow (BM) and the secondary lymphoid organs. The aim of this study was to assess the number and phenotype of circulating B cell in untreated IBD patients and their counterparts treated with biological anti-TNF drugs. METHODS: The study involved 13 untreated IBD patients, 36 IBD patients treated with biological drugs, and 10 healthy controls. The B cell phenotypes were assessed by means of flow cytometry using monoclonal antibodies specific for CD20, CD19, CD3, CD27 and CD43. In order to evaluate B cell development in bone marrow and peripheral B cell activation, we identified four B cell subsets: hematogones (HBs: CD20+19+3-27-43+), memory B cells (MBs: CD20+19+3-27+43-), pre-plasmablasts (PPBs: CD20+19+3-27+43+), and plasmablasts (PBs: CD20-19+3-27+43+). RESULTS: The total number of B cells in the untreated patients was three times lower than that in the patients treated with biological drug (p