title: B cells regulate CD4+ T cell responses to papain following B cell receptor-independent papain uptake.
abstract: Papain, a cysteine protease allergen with inherent adjuvant activity, induces potent IL-4 expression by T cells in the popliteal lymph nodes of mice following footpad immunization. In this study, we identify a novel, non-BCR-mediated capacity for B cells to rapidly bind and internalize papain. B cells subsequently regulate the adaptive immune response by enhancing ICOS expression on CD4(+) T cells and amplifying Th2 and follicular helper T cell induction. Ab blockade of ICOS ligand, expressed by popliteal lymph node B cells, but not dendritic cells, at the peak of the response inhibits IL-4 responses in wild-type mice but not B cell-deficient mice. Thus, B cells play a critical role in amplifying adjuvant-dependent Th2 polarization following noncanonical acquisition and internalization of the cysteine protease papain.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; and.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Dwyer
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Woodruff
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; and.
authors.forename: K Frank
authors.initials: KF
authors.lastname: Austen
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; and mgurish@partners.org.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gurish
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D007114:Immunization / Q000379:methods; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D010206:Papain / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4; D010206:Papain