Craig brooks
Faculty Member
Last active: 3/14/2019

TIM-1 signaling is required for maintenance and induction of regulatory B cells.

Yeung MY, Ding Q, Brooks CR, Xiao S, Workman CJ, Vignali DA, Ueno T, Padera RF, Kuchroo VK, Najafian N, Rothstein DM
Am J Transplant. 2015 15 (4): 942-53

PMID: 25645598 · PMCID: PMC4530122 · DOI:10.1111/ajt.13087

Apart from their role in humoral immunity, B cells can exhibit IL-10-dependent regulatory activity (Bregs). These regulatory subpopulations have been shown to inhibit inflammation and allograft rejection. However, our understanding of Bregs has been hampered by their rarity, lack of a specific marker, and poor insight into their induction and maintenance. We previously demonstrated that T cell immunoglobulin mucin domain-1 (TIM-1) identifies over 70% of IL-10-producing B cells, irrespective of other markers. We now show that TIM-1 is the primary receptor responsible for Breg induction by apoptotic cells (ACs). However, B cells that express a mutant form of TIM-1 lacking the mucin domain (TIM-1(Δmucin) ) exhibit decreased phosphatidylserine binding and are unable to produce IL-10 in response to ACs or by specific ligation with anti-TIM-1. TIM-1(Δmucin) mice also exhibit accelerated allograft rejection, which appears to be due in part to their defect in both baseline and induced IL-10(+) Bregs, since a single transfer of WT TIM-1(+) B cells can restore long-term graft survival. These data suggest that TIM-1 signaling plays a direct role in Breg maintenance and induction both under physiological conditions (in response to ACs) and in response to therapy through TIM-1 ligation. Moreover, they directly demonstrate that the mucin domain regulates TIM-1 signaling.

© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

MeSH Terms (9)

Animals B-Lymphocytes, Regulatory Graft Survival Hepatitis A Virus Cellular Receptor 1 Interleukin-10 Membrane Proteins Mice Mice, Inbred BALB C Signal Transduction

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