Nonredundant roles for B cell-derived IL-10 in immune counter-regulation. 2009

Rajat Madan, and Filiz Demircik, and Sangeetha Surianarayanan, and Jessica L Allen, and Senad Divanovic, and Aurelien Trompette, and Nir Yogev, and Yuanyuan Gu, and Marat Khodoun, and David Hildeman, and Nicholas Boespflug, and Mariela B Fogolin, and Lothar Gröbe, and Marina Greweling, and Fred D Finkelman, and Rhonda Cardin, and Markus Mohrs, and Werner Müller, and Ari Waisman, and Axel Roers, and Christopher L Karp
Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.

IL-10 plays a central role in restraining the vigor of inflammatory responses, but the critical cellular sources of this counter-regulatory cytokine remain speculative in many disease models. Using a novel IL-10 transcriptional reporter mouse, we found an unexpected predominance of B cells (including plasma cells) among IL-10-expressing cells in peripheral lymphoid tissues at baseline and during diverse models of in vivo immunological challenge. Use of a novel B cell-specific IL-10 knockout mouse revealed that B cell-derived IL-10 nonredundantly decreases virus-specific CD8(+) T cell responses and plasma cell expansion during murine cytomegalovirus infection and modestly restrains immune activation after challenge with foreign Abs to IgD. In contrast, no role for B cell-derived IL-10 was evident during endotoxemia; however, although B cells dominated lymphoid tissue IL-10 production in this model, myeloid cells were dominant in blood and liver. These data suggest that B cells are an underappreciated source of counter-regulatory IL-10 production in lymphoid tissues, provide a clear rationale for testing the biological role of B cell-derived IL-10 in infectious and inflammatory disease, and underscore the utility of cell type-specific knockouts for mechanistic limning of immune counter-regulation.

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008221 Lymphoid Tissue Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS. Lymphatic Tissue,Lymphatic Tissues,Lymphoid Tissues,Tissue, Lymphatic,Tissue, Lymphoid,Tissues, Lymphatic,Tissues, Lymphoid
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D006566 Herpesviridae Infections Virus diseases caused by the HERPESVIRIDAE. Herpesvirus Infections,B Virus Infection,Infections, Herpesviridae,Infections, Herpesvirus,B Virus Infections,Herpesviridae Infection,Herpesvirus Infection,Infection, B Virus,Infection, Herpesviridae,Infection, Herpesvirus,Infections, B Virus
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016175 B-Lymphocyte Subsets A classification of B-lymphocytes based on structurally or functionally different populations of cells. B-Cell Subsets,Tumor-Infiltrating B Cells,Tumor-Infiltrating B Lymphocytes,B Effector 1 Cells,B Effector 2 Cells,B-1 Cells,B-1 Lymphocytes,B-2 Lymphocytes,B-Lymphocytes, Effector,B1 Lymphocytes,B2 Lymphocytes,Be1 Cells,Be2 Cells,Effector B Cells,B 1 Cells,B 1 Lymphocytes,B 2 Lymphocytes,B Cell Subsets,B Cell, Tumor-Infiltrating,B Lymphocyte Subsets,B Lymphocyte, Tumor-Infiltrating,B-1 Cell,B-1 Lymphocyte,B-2 Lymphocyte,B-Cell Subset,B-Lymphocyte Subset,B-Lymphocyte, Effector,B1 Lymphocyte,B2 Lymphocyte,Be1 Cell,Be2 Cell,Cell, B-1,Cell, Be1,Cell, Be2,Effector B Cell,Effector B-Lymphocyte,Effector B-Lymphocytes,Lymphocyte, B-1,Lymphocyte, B-2,Lymphocyte, B1,Lymphocyte, B2,Tumor Infiltrating B Cells,Tumor Infiltrating B Lymphocytes,Tumor-Infiltrating B Cell,Tumor-Infiltrating B Lymphocyte

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