Unexpected role for the immunoproteasome subunit LMP2 in antiviral humoral and innate immune responses.

TitleUnexpected role for the immunoproteasome subunit LMP2 in antiviral humoral and innate immune responses.
Publication TypeJournal Article
Year of Publication2010
AuthorsHensley SE, Zanker D, Dolan BP, David A, Hickman HD, Embry AC, Skon CN, Grebe KM, Griffin TA, Chen W, Bennink JR, Yewdell JW
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume184
Issue8
Pagination4115-22
Date Published2010 Apr 15
ISSN1550-6606
KeywordsAnimals, Antibodies, Viral, Antigen Presentation, B-Lymphocytes, Cells, Cultured, Cysteine Endopeptidases, Dendritic Cells, Immunity, Innate, Influenza A virus, Mice, Mice, Congenic, Mice, Inbred C57BL, Mice, Knockout, NF-kappa B, Proteasome Endopeptidase Complex, Protein Subunits, Signal Transduction
Abstract

Proteasomes are multisubunit proteases that initiate degradation of many Ags presented by MHC class I molecules. Vertebrates express alternate forms of each of the three catalytic proteasome subunits: standard subunits, and immunosubunits, which are constitutively expressed by APCs and are induced in other cell types by exposure to cytokines. The assembly of mixed proteasomes containing standard subunits and immunosubunits is regulated in a tissue specific manner. In this study, we report that the presence of mixed proteasomes in immune cells in LMP2(-/-) mice compromises multiple components that contribute to the generation of antiviral Ab responses, including splenic B cell numbers, survival and function of adoptively transferred B cells, Th cell function, and dendritic cell secretion of IL-6, TNF-alpha, IL-1beta, and type I IFNs. These defects did not result from compromised overall protein degradation, rather they were associated with altered NF-kappaB activity. These findings demonstrate an important role for immunoproteasomes in immune cell function beyond their contribution to Ag processing.

DOI10.4049/jimmunol.0903003
Alternate JournalJ. Immunol.