Publication Date:
2012-10-16
Description:
B cells regulate immune responses by producing antigen-specific antibodies. However, specific B-cell subsets can also negatively regulate T-cell immune responses, and have been termed regulatory B cells. Human and mouse regulatory B cells (B10 cells) with the ability to express the inhibitory cytokine interleukin-10 (IL-10) have been identified. Although rare, B10 cells are potent negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases in mice. How B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression is unknown. Using a mouse model for multiple sclerosis, here we show that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells. Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion by four-million-fold, and generate B10 effector cells producing IL-10 that markedly inhibit disease symptoms when transferred into mice with established autoimmune disease. The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493692/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493692/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoshizaki, Ayumi -- Miyagaki, Tomomitsu -- DiLillo, David J -- Matsushita, Takashi -- Horikawa, Mayuka -- Kountikov, Evgueni I -- Spolski, Rosanne -- Poe, Jonathan C -- Leonard, Warren J -- Tedder, Thomas F -- AI057157/AI/NIAID NIH HHS/ -- AI56363/AI/NIAID NIH HHS/ -- U19 AI056363/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2012 Nov 8;491(7423):264-8. doi: 10.1038/nature11501. Epub 2012 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23064231" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD19/genetics/metabolism
;
Antigens, CD40/immunology/metabolism
;
Antigens, CD5/metabolism
;
Autoimmunity/*immunology
;
B-Lymphocytes, Regulatory/cytology/*immunology/metabolism/secretion
;
Cell Division
;
Disease Models, Animal
;
Encephalomyelitis, Autoimmune, Experimental/immunology/pathology
;
Female
;
Histocompatibility Antigens Class II/immunology
;
Humans
;
Interleukin-10/biosynthesis/immunology/secretion
;
Interleukins/*immunology
;
Mice
;
Mice, Inbred C57BL
;
Multiple Sclerosis/immunology/pathology
;
Receptors, Interleukin-21/immunology/metabolism
;
T-Lymphocytes/*immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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