Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice
Qing Ding, … , Nader Najafian, David M. Rothstein
Qing Ding, … , Nader Najafian, David M. Rothstein
Published August 8, 2011
Citation Information: J Clin Invest. 2011;121(9):3645-3656. https://doi.org/10.1172/JCI46274.
View: Text | PDF
Research Article Immunology Article has an altmetric score of 7

Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice

  • Text
  • PDF
Abstract

T cell Ig domain and mucin domain protein 1 (TIM-1) is a costimulatory molecule that regulates immune responses by modulating CD4+ T cell effector differentiation. However, the function of TIM-1 on other immune cell populations is unknown. Here, we show that in vivo in mice, TIM-1 is predominantly expressed on B rather than T cells. Importantly, TIM-1 was expressed by a large majority of IL-10–expressing regulatory B cells in all major B cell subpopulations, including transitional, marginal zone, and follicular B cells, as well as the B cell population characterized as CD1dhiCD5+. A low-affinity TIM-1–specific antibody that normally promotes tolerance in mice, actually accelerated (T cell–mediated) immune responsiveness in the absence of B cells. TIM-1+ B cells were highly enriched for IL-4 and IL-10 expression, promoted Th2 responses, and could directly transfer allograft tolerance. Both cytokine expression and number of TIM-1+ regulatory B cells (Bregs) were induced by TIM-1–specific antibody, and this was dependent on IL-4 signaling. Thus, TIM-1 is an inclusive marker for IL-10+ Bregs that can be induced by TIM-1 ligation. These findings suggest that TIM-1 may be a novel therapeutic target for modulating the immune response and provide insight into the signals involved in the generation and induction of Bregs.

Authors

Qing Ding, Melissa Yeung, Geoffrey Camirand, Qiang Zeng, Hisaya Akiba, Hideo Yagita, Geetha Chalasani, Mohamed H. Sayegh, Nader Najafian, David M. Rothstein

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2009 Total
Citations: 9 14 10 16 21 20 18 16 20 25 18 23 17 14 4 1 246
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2014 (23)

Title and authors Publication Year
B cells mediate chronic allograft rejection independent of antibody production
Qiang Zeng, Yue-Harn Ng, Tripti Singh, Ke Jiang, Khaleefathullah Sheriff, Renee Ippolito, Salwa Zahalka, Qi Li, Parmjeet Randhawa, Rosemary A. Hoffman, Balathiripurasundari Ramaswami, Frances Lund, Geetha Chalasani
Journal of Clinical Investigation 2014
Interleukin-10 + Regulatory B Cells Arise Within Antigen-Experienced CD40 + B Cells to Maintain Tolerance to Islet Autoantigens
S Kleffel, A Vergani, S Tezza, MB Nasr, MA Niewczas, S Wong, R Bassi, F D’Addio, T Schatton, R Abdi, M Atkinson, MH Sayegh, L Wen, CH Wasserfall, KC O’Connor, P Fiorina
Diabetes 2014
Transplantation tolerance and its outcome during infections and inflammation
AS Chong, ML Alegre
Immunological Reviews 2014
The First US Domestic Report of Disseminated Mycobacterium avium Complex and Anti-Interferon-γ Autoantibodies
E OConnell, LB Rosen, RW LaRue, V Fabre, MT Melia, PG Auwaerter, SM Holland, SK Browne
Journal of Clinical Immunology 2014
The roles of regulatory B cells in cancer
Y He, H Qian, Y Liu, L Duan, Y Li, G Shi
Journal of Immunology Research 2014
Interleukin-35 induces regulatory B cells that suppress autoimmune disease
RX Wang, CR Yu, IM Dambuza, RM Mahdi, MB Dolinska, YV Sergeev, PT Wingfield, SH Kim, CE Egwuagu
Nature Medicine 2014
Regulatory B cells: an exciting target for future therapeutics in transplantation
A Nouël, Q Simon, C Jamin, JO Pers, S Hillion
Frontiers in immunology 2014
Infiltrating Regulatory B Cells Control Neuroinflammation following Viral Brain Infection
MB Mutnal, S Hu, SJ Schachtele, JR Lokensgard
Journal of immunology (Baltimore, Md. : 1950) 2014
Immunologic Human Renal Allograft Injury Associates with an Altered IL-10/TNF-  Expression Ratio in Regulatory B Cells
A Cherukuri, DM Rothstein, B Clark, CR Carter, A Davison, M Hernandez-Fuentes, E Hewitt, AD Salama, RJ Baker
Journal of the American Society of Nephrology : JASN 2014
Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis
C Xing, N Ma, H Xiao, X Wang, M Zheng, G Han, G Chen, C Hou, B Shen, Y Li, R Wang
Journal of leukocyte biology 2014
Regulatory B Cells
G Vitale, F Mion
2014
B cells with immune-regulating function in transplantation
J Stolp, LA Turka, KJ Wood
Nature Reviews Nephrology 2014
B Cells and Kidney Transplantation: Beyond Antibodies
A Mehrotra, PS Heeger
Journal of the American Society of Nephrology : JASN 2014
IL-10-producing B cells are induced early in HIV-1 infection and suppress HIV-1-specific T cell responses
J Liu, W Zhan, CJ Kim, K Clayton, H Zhao, E Lee, JC Cao, B Ziegler, A Gregor, FY Yue, S Huibner, S MacParland, J Schwartz, HH Song, E Benko, G Gyenes, C Kovacs, R Kaul, M Ostrowski
PloS one 2014
IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut
S Sattler, GS Ling, D Xu, L Hussaarts, A Romaine, H Zhao, L Fossati-Jimack, T Malik, HT Cook, M Botto, YL Lau, HH Smits, FY Liew, FP Huang
Journal of Autoimmunity 2014
TGF-β-producing regulatory B cells induce regulatory T cells and promote transplantation tolerance: Immunomodulation
KM Lee, RT Stott, G Zhao, J SooHoo, W Xiong, MM Lian, L Fitzgerald, S Shi, E Akrawi, J Lei, S Deng, H Yeh, JF Markmann, JI Kim
European Journal of Immunology 2014
AST Cutting Edge of Transplantation 2013 Meeting Report: A Comprehensive Look at B Cells and Antibodies in Transplantation: AST Cutting Edge of Transplantation 2013
M Mengel, A Chong, DM Rothstein, E Zorn, JS Maltzman
American Journal of Transplantation 2014
Regulatory B Cells Are Inversely Associated with Disease Activity in Rheumatoid Arthritis
J Kim, HJ Lee, IS Yoo, SW Kang, JH Lee
Yonsei Medical Journal 2014
Role of IL-10-Producing Regulatory B Cells in Chronic Hepatitis B Virus Infection
Y Gong, C Zhao, P Zhao, M Wang, G Zhou, F Han, Y Cui, J Qian, H Zhang, H Xiong, J Sheng, T Jiang
Digestive Diseases and Sciences 2014
Regulatory B cells are induced by gut microbiota–driven interleukin-1β and interleukin-6 production
EC Rosser, K Oleinika, S Tonon, R Doyle, A Bosma, NA Carter, KA Harris, SA Jones, N Klein, C Mauri
Nature Medicine 2014
Insulin-like Growth Factor-2 Enhances Functions of Antigen (Ag)-specific Regulatory B Cells
XR Geng, G Yang, M Li, JP Song, ZQ Liu, S Qiu, Z Liu, PC Yang
The Journal of biological chemistry 2014
Interleukin-35 takes the 'B' line
C Mauri, K Nistala
Nature Medicine 2014
TIM4 regulates the anti-islet Th2 alloimmune response
Vergani A, Gatti F, Lee KM, D\u2019Addio F, Tezza S, Chin M, Bassi R, Tian Z, Wu E, Maffi P, Nasr MB, Kim JI, Secchi A, Markmann JF, Rothstein DM, Turka LA, Sayegh MH, Fiorina P
Cell transplantation 2014

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 1 policy sources
Referenced in 1 patents
On 1 Facebook pages
213 readers on Mendeley
1 readers on CiteULike
See more details