Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice
Open Access
- 1 September 2011
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 121 (9), 3645-3656
- https://doi.org/10.1172/jci46274
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.Keywords
This publication has 43 references indexed in Scilit:
- Novel Suppressive Function of Transitional 2 B Cells in Experimental ArthritisThe Journal of Immunology, 2007
- Efficacy of B-Cell–Targeted Therapy with Rituximab in Patients with Rheumatoid ArthritisThe New England Journal of Medicine, 2004
- Identification of B-Cell SubsetsPublished by Springer Science and Business Media LLC ,2004
- Cutting Edge: Transplantation Tolerance through Enhanced CTLA-4 ExpressionThe Journal of Immunology, 2003
- Prevention of Arthritis by Interleukin 10–producing B CellsThe Journal of Experimental Medicine, 2003
- B cells regulate autoimmunity by provision of IL-10Nature Immunology, 2002
- Islet filtration: a simple and rapid new purification procedure that avoids ficoll and improves islet mass and function.Transplantation, 2002
- Critical role of B cells in the development of T cell tolerance to aeroallergensInternational Immunology, 2002
- Chronic Intestinal Inflammatory Condition Generates IL-10-Producing Regulatory B Cell Subset Characterized by CD1d UpregulationImmunity, 2002
- Reciprocal regulation of polarized cytokine production by effector B and T cellsNature Immunology, 2000