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Tofacitinib, a JAK inhibitor, inhibits human B cell activation in vitro
  1. Sheau-Pey Wang,
  2. Shigeru Iwata,
  3. Shingo Nakayamada,
  4. Kei Sakata,
  5. Kunihiro Yamaoka,
  6. Yoshiya Tanaka
  1. The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan
  1. Correspondence to Professor Yoshiya Tanaka, The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan; tanaka{at}med.uoeh-u.ac.jp

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B cells initiate and perpetuate autoimmune disease processes. Interleukin (IL)-4 and IL-21 produced by follicular helper T cells are required for B cell activation, germinal centre formation, immunoglobulin class switching and plasma cell differentiation.1 ,2 The JAK inhibitor tofacitinib is approved for treatment of rheumatoid arthritis. We recently reported that tofacitinib can suppress IL-17 and interferon-γ production by CD4+ T cells3 and inhibit the T cell stimulatory capacity of human monocyte-derived dendritic cells.4 However, whether this action involves B cell activation remains unclear.

Here we investigated the in vitro effects of tofacitinib on the gene regulatory network that controls B cell class switching and differentiation. Purified CD19+ B cells were stimulated with B cell antigen receptor (BCR), soluble CD40 ligand (sCD40L) and cytokines with/without tofacitinib. Culture medium was replenished on day 3. Cell viability tests revealed that, although B cell survival decreased considerably over time, the possibility of pharmacological toxicity by tofacitinib could be excluded (data not shown).

The expression of AICDA was slightly induced by cytokines or BCR/sCD40L alone, while costimulation with BCR, sCD40L and cytokines, especially IL-4, caused robust gene expression (figure 1A). BCL6 and XBP-1 exhibited similar expression patterns, …

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