Abstract
In tonsils, CD138(+) plasma cells (PCs) are surrounded by CD163(+) resident macrophages (Ms). We show here that human Ms (isolated from tonsils or generated from monocytes in vitro) drive activated B cells to differentiate into CD138(+)CD38(++) PCs through secreted CXCL10/IP-10 and VCAM-1 contact. IP-10 production by Ms is induced by B cell-derived IL-6 and depends on STAT3 phosphorylation. Furthermore, IP-10 amplifies the production of IL-6 by B cells, which sustains the STAT3 signals that lead to PC differentiation. IP-10-deficient mice challenged with NP-Ficoll show a decreased frequency of NP-specific PCs and lower titers of antibodies. Thus, our results reveal a novel dialog between Ms and B cells, in which IP-10 acts as a PC differentiation factor.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies / immunology
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Antigens / immunology
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Antigens, CD / metabolism
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Antigens, Differentiation, Myelomonocytic / metabolism
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Cell Communication
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Cell Differentiation / immunology*
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Chemokine CXCL10 / biosynthesis
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Chemokine CXCL10 / metabolism*
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Child
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Child, Preschool
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Humans
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Immunoglobulin Class Switching / immunology
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Immunoglobulin G / biosynthesis
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Immunologic Memory
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Interleukin-6 / metabolism
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Macrophages / immunology*
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Macrophages / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Palatine Tonsil / immunology
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Palatine Tonsil / metabolism
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Phosphorylation
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Plasma Cells / cytology*
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Plasma Cells / immunology*
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Receptors, Cell Surface / metabolism
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STAT3 Transcription Factor / metabolism
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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Antibodies
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Antigens
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Antigens, CD
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Antigens, Differentiation, Myelomonocytic
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CD163 antigen
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Chemokine CXCL10
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Immunoglobulin G
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Interleukin-6
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Receptors, Cell Surface
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STAT3 Transcription Factor
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Vascular Cell Adhesion Molecule-1