Article Text

THU0183 Treatment with Tofacitinib Inhibits Human Naïve B Lymphocyte Development and Function In Vitro
  1. J. Thiel,
  2. K. Fischer,
  3. R.E. Voll,
  4. R. Lorenzetti,
  5. B. Bannert,
  6. N. Venhoff,
  7. M. Rizzi
  1. Rheumatology/Clinical Immunology, University Hospital Freiburg, Freiburg, Germany


Background B cells are pivotal to the pathogenesis of many autoimmune diseases including rheumatoid arthritis (RA). Tofacitinib, a JAK inhibitor, is effective and safe in the treatment of RA. Tofacitinib interferes with signal transduction via cytokine receptors using the common γ-chain.

Objectives Despite of extensive data on T lymphocytes, the impact of tofacitinib on B lymphocytes is poorly understood. In this study we assess the effect of tofacitinib on the differentiation of naive B-lymphocytes and their function.

Methods Sorted human B cells from cord blood or buffy coat were stimulated in the presence of increasing doses of tofacitinib. B cell phenotypes were determined by flow cytometry. Immunoglobulin concentrations were measured by ELISA. The expression of B cell fate determining genes PRDM1, IRF4, XBP1, and AICDA was analyzed by quantitative RT-PCR.

Results Tofacitinib treatment strongly impaired plasmablast development, immunoglobulin secretion and induction of PRDM1, IRF-4, and XBP-1 from naive B cells. Interestingly, class switch and AICDA induction from activated naive B cells was only slightly reduced. B cells purified from buffy coats, including naive and memory B cells, stimulated in the presence of tofacitinib, showed only a moderate reduction in plasmablast formation, immunoglobulin secretion and proliferation.

Conclusions We demonstrated that tofacitinib has a direct impact on human naive B-lymphocytes, independently from its effect on T lymphocytes, by impairing their development into plasmablasts and immunoglobulin secretion. Tofacitinib predominantly affects naive B lymphocytes, while its effect on total peripheral B cells containing naive and memory B cells is less pronounced. Our data are of clinical importance as they suggest that vaccinations should be performed prior to tofacitinib treatment. Furthermore, impairement of B cell function by tofacitimib may directly contribute to its therapeutic effects. This fact has implications for the potential use of tofacitinib in B cell-mediated diseases.

Disclosure of Interest None declared

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.