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Bob1 limits cellular frequency of T‐follicular helper cells

T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B‐cell lymphoma‐6 and Blimp‐1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique me...

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Autores principales: Yamashita, Keiji, Kawata, Koji, Matsumiya, Hiroshi, Kamekura, Ryuta, Jitsukawa, Sumito, Nagaya, Tomonori, Ogasawara, Noriko, Takano, Ken‐ichi, Kubo, Terufumi, Kimura, Sachiko, Shigehara, Katsunori, Himi, Tetsuo, Ichimiya, Shingo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084739/
https://www.ncbi.nlm.nih.gov/pubmed/27080143
http://dx.doi.org/10.1002/eji.201545499
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author Yamashita, Keiji
Kawata, Koji
Matsumiya, Hiroshi
Kamekura, Ryuta
Jitsukawa, Sumito
Nagaya, Tomonori
Ogasawara, Noriko
Takano, Ken‐ichi
Kubo, Terufumi
Kimura, Sachiko
Shigehara, Katsunori
Himi, Tetsuo
Ichimiya, Shingo
author_facet Yamashita, Keiji
Kawata, Koji
Matsumiya, Hiroshi
Kamekura, Ryuta
Jitsukawa, Sumito
Nagaya, Tomonori
Ogasawara, Noriko
Takano, Ken‐ichi
Kubo, Terufumi
Kimura, Sachiko
Shigehara, Katsunori
Himi, Tetsuo
Ichimiya, Shingo
author_sort Yamashita, Keiji
collection PubMed
description T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B‐cell lymphoma‐6 and Blimp‐1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh‐cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of B‐cell lymphoma‐6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1(−/−) mice were much higher than those in wild‐type (WT) mice. In addition, expansion of Tfh cells within Bob1(−/−)CD4(+) T cells transferred into WT mice revealed that the high frequency of Tfh cells was caused by a T‐cell‐intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1(−/−) Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody and were also refractory to CD3‐induced cell death in comparison to WT Tfh cells. These results suggest that Tfh cells harbor a Bob1‐related mechanism to restrict numerical frequency against stimulation of TCRs.
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spelling pubmed-50847392016-11-09 Bob1 limits cellular frequency of T‐follicular helper cells Yamashita, Keiji Kawata, Koji Matsumiya, Hiroshi Kamekura, Ryuta Jitsukawa, Sumito Nagaya, Tomonori Ogasawara, Noriko Takano, Ken‐ichi Kubo, Terufumi Kimura, Sachiko Shigehara, Katsunori Himi, Tetsuo Ichimiya, Shingo Eur J Immunol Cellular Immune Response T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B‐cell lymphoma‐6 and Blimp‐1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh‐cell identity. In this study, we found that Tfh cells preferentially express the transcriptional coactivator Bob1. Bob1 of Tfh cells was dispensable for the expression of B‐cell lymphoma‐6 and the functional property of the cells for B cell help. However, upon initial immunization of foreign antigens, the percentages of Tfh cells in Bob1(−/−) mice were much higher than those in wild‐type (WT) mice. In addition, expansion of Tfh cells within Bob1(−/−)CD4(+) T cells transferred into WT mice revealed that the high frequency of Tfh cells was caused by a T‐cell‐intrinsic mechanism. These findings were further supported by the results of in vitro studies demonstrating that Bob1(−/−) Tfh cells had greater proliferative activity in response to stimuli by CD3/CD28 monoclonal antibody and were also refractory to CD3‐induced cell death in comparison to WT Tfh cells. These results suggest that Tfh cells harbor a Bob1‐related mechanism to restrict numerical frequency against stimulation of TCRs. John Wiley and Sons Inc. 2016-05-03 2016-06 /pmc/articles/PMC5084739/ /pubmed/27080143 http://dx.doi.org/10.1002/eji.201545499 Text en © 2016 The Authors. European Journal of Immunology published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Cellular Immune Response
Yamashita, Keiji
Kawata, Koji
Matsumiya, Hiroshi
Kamekura, Ryuta
Jitsukawa, Sumito
Nagaya, Tomonori
Ogasawara, Noriko
Takano, Ken‐ichi
Kubo, Terufumi
Kimura, Sachiko
Shigehara, Katsunori
Himi, Tetsuo
Ichimiya, Shingo
Bob1 limits cellular frequency of T‐follicular helper cells
title Bob1 limits cellular frequency of T‐follicular helper cells
title_full Bob1 limits cellular frequency of T‐follicular helper cells
title_fullStr Bob1 limits cellular frequency of T‐follicular helper cells
title_full_unstemmed Bob1 limits cellular frequency of T‐follicular helper cells
title_short Bob1 limits cellular frequency of T‐follicular helper cells
title_sort bob1 limits cellular frequency of t‐follicular helper cells
topic Cellular Immune Response
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084739/
https://www.ncbi.nlm.nih.gov/pubmed/27080143
http://dx.doi.org/10.1002/eji.201545499
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