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Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis.
J Immunol. 2010 Aug 15; 185(4):2240-52.JI

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a T lymphocyte-mediated autoimmune disease of the CNS. Significant roles for B cells and a rare IL-10-producing CD1d(high)CD5(+) regulatory B cell subset (B10 cells) have been identified during the initiation and progression of EAE. Whether and how the regulatory functions of B10 cells and FoxP3(+) T regulatory cells (Tregs) overlap or influence EAE immunopathogenesis independently has remained unanswered. This study demonstrates that the number of endogenous or adoptively transferred B10 cells directly influenced EAE pathogenesis through their production of IL-10. B10 cell numbers expanded quickly within the spleen, but not CNS following myelin oligodendrocyte glycoprotein(35-55) immunization, which paralleled B10 cell regulation of disease initiation. The adoptive transfer of myelin oligodendrocyte glycoprotein(33-35)-sensitized B10 cells into wild-type mice reduced EAE initiation dramatically. However, B10 cells did not suppress ongoing EAE disease. Rather, Treg numbers expanded significantly within the CNS during disease progression, which paralleled their negative regulation of late-phase disease. Likewise, the preferential depletion of B10 cells in vivo during disease initiation enhanced EAE pathogenesis, whereas Treg depletion enhanced late-phase disease. B10 cells did not regulate T cell proliferation during in vitro assays, but significantly altered CD4(+) T cell IFN-gamma and TNF-alpha production. Furthermore, B10 cells downregulated the ability of dendritic cells to act as APCs and thereby indirectly modulated T cell proliferation. Thus, B10 cells predominantly control disease initiation, whereas Tregs reciprocally inhibit late-phase disease, with overlapping B10 cell and Treg functions shaping the normal course of EAE immunopathogenesis.

Authors+Show Affiliations

Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20624940

Citation

Matsushita, Takashi, et al. "Regulatory B Cells (B10 Cells) and Regulatory T Cells Have Independent Roles in Controlling Experimental Autoimmune Encephalomyelitis Initiation and Late-phase Immunopathogenesis." Journal of Immunology (Baltimore, Md. : 1950), vol. 185, no. 4, 2010, pp. 2240-52.
Matsushita T, Horikawa M, Iwata Y, et al. Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. J Immunol. 2010;185(4):2240-52.
Matsushita, T., Horikawa, M., Iwata, Y., & Tedder, T. F. (2010). Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. Journal of Immunology (Baltimore, Md. : 1950), 185(4), 2240-52. https://doi.org/10.4049/jimmunol.1001307
Matsushita T, et al. Regulatory B Cells (B10 Cells) and Regulatory T Cells Have Independent Roles in Controlling Experimental Autoimmune Encephalomyelitis Initiation and Late-phase Immunopathogenesis. J Immunol. 2010 Aug 15;185(4):2240-52. PubMed PMID: 20624940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. AU - Matsushita,Takashi, AU - Horikawa,Mayuka, AU - Iwata,Yohei, AU - Tedder,Thomas F, Y1 - 2010/07/12/ PY - 2010/7/14/entrez PY - 2010/7/14/pubmed PY - 2010/9/24/medline SP - 2240 EP - 52 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 185 IS - 4 N2 - Experimental autoimmune encephalomyelitis (EAE) is a T lymphocyte-mediated autoimmune disease of the CNS. Significant roles for B cells and a rare IL-10-producing CD1d(high)CD5(+) regulatory B cell subset (B10 cells) have been identified during the initiation and progression of EAE. Whether and how the regulatory functions of B10 cells and FoxP3(+) T regulatory cells (Tregs) overlap or influence EAE immunopathogenesis independently has remained unanswered. This study demonstrates that the number of endogenous or adoptively transferred B10 cells directly influenced EAE pathogenesis through their production of IL-10. B10 cell numbers expanded quickly within the spleen, but not CNS following myelin oligodendrocyte glycoprotein(35-55) immunization, which paralleled B10 cell regulation of disease initiation. The adoptive transfer of myelin oligodendrocyte glycoprotein(33-35)-sensitized B10 cells into wild-type mice reduced EAE initiation dramatically. However, B10 cells did not suppress ongoing EAE disease. Rather, Treg numbers expanded significantly within the CNS during disease progression, which paralleled their negative regulation of late-phase disease. Likewise, the preferential depletion of B10 cells in vivo during disease initiation enhanced EAE pathogenesis, whereas Treg depletion enhanced late-phase disease. B10 cells did not regulate T cell proliferation during in vitro assays, but significantly altered CD4(+) T cell IFN-gamma and TNF-alpha production. Furthermore, B10 cells downregulated the ability of dendritic cells to act as APCs and thereby indirectly modulated T cell proliferation. Thus, B10 cells predominantly control disease initiation, whereas Tregs reciprocally inhibit late-phase disease, with overlapping B10 cell and Treg functions shaping the normal course of EAE immunopathogenesis. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/20624940/Regulatory_B_cells__B10_cells__and_regulatory_T_cells_have_independent_roles_in_controlling_experimental_autoimmune_encephalomyelitis_initiation_and_late_phase_immunopathogenesis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=20624940 DB - PRIME DP - Unbound Medicine ER -