TSLP or IL-7 provide an IL-7Rα signal that is critical for human B lymphopoiesis

Terry Ann M. Milford, Ruijun J. Su, Olivia L. Francis, Ineavely Baez, Shannalee R. Martinez, Jacqueline S. Coats, Abby J. Weldon, Milcris N. Calderon, Michael C. Nwosu, Allen R. Botimer, Batul T. Suterwala, Xiao Bing Zhang, Christopher L. Morris, David J. Weldon, Sinisa Dovat, Kimberly J. Payne

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Abstract

Thymic stromal lymphopoietin (TSLP) and IL-7 are cytokines that signal via the IL-7 receptor alpha (IL-7Rα) to exert both overlapping and unique functions during early stages of mouse B-cell development. In human B lymphopoiesis, the requirement for IL-7Rα signaling is controversial and the roles of IL-7 and TSLP are less clear. Here, we evaluated human B-cell production using novel in vitro and xenograft models of human B-cell development that provide selective IL-7 and human TSLP (hTSLP) stimulation. We show that in vitro human B-cell production is almost completely blocked in the absence of IL-7Rα stimulation, and that either TSLP or IL-7 can provide a signal critical for the production and proliferation of human CD19+ PAX5+ pro-B cells. Analysis of primary human bone marrow stromal cells shows that they express both IL-7 and TSLP, providing an in vivo source of these cytokines. We further show that the in vivo production of human pro-B cells under the influence of mouse IL-7 in a xenograft scenario is reduced by anti-IL-7 neutralizing antibodies, and that this loss can be restored by hTSLP at physiological levels. These data establish the importance of IL-7Rα mediated signals for normal human B-cell production.

Original languageEnglish (US)
Pages (from-to)2155-2161
Number of pages7
JournalEuropean Journal of Immunology
Volume46
Issue number9
DOIs
StatePublished - Sep 1 2016

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Milford, T. A. M., Su, R. J., Francis, O. L., Baez, I., Martinez, S. R., Coats, J. S., Weldon, A. J., Calderon, M. N., Nwosu, M. C., Botimer, A. R., Suterwala, B. T., Zhang, X. B., Morris, C. L., Weldon, D. J., Dovat, S., & Payne, K. J. (2016). TSLP or IL-7 provide an IL-7Rα signal that is critical for human B lymphopoiesis. European Journal of Immunology, 46(9), 2155-2161. https://doi.org/10.1002/eji.201646307