Cutting edge: human B cell function is regulated by interaction with soluble CD14: opposite effects on IgG1 and IgE production.
The mechanism(s) controlling activation of naive B cells, their proliferation, Ag receptor affinity maturation, isotype switching, and their fate as memory or plasma cells is not fully elucidated. Here we show that between 24 and 60% of CD19+ cells in PBMC bind soluble CD14 (sCD14). Tonsillar B cells also bind sCD14, but preferentially the CD38-ve/low cells. Interaction of sCD14 with B cells resulted in higher levels of IgG1 and marked inhibition of IgE production by activated tonsillar B cells and Ag-stimulated PBMC. We found that sCD14 interfered with CD40 signaling in B cells, inhibited IL-6 production by activated B cells, and increased the kinetics and magnitude of CD40 ligand expression on T cells. Together with the previously reported effects on T cells, these findings define sCD14 as a novel soluble regulatory factor capable of modulating cellular and humoral immune responses by interacting directly with T and B cells.
Arias
M A
MA
Department of Medicine, University of Wales, College of Medicine, Cardiff, United Kingdom.
Rey Nores
J E
JE
Vita
N
N
Stelter
F
F
Borysiewicz
L K
LK
Ferrara
P
P
Labéta
M O
MO
D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism / Q000502:physiology; D023201:CD40 Ligand; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D000072000:NF-KappaB Inhibitor alpha; D014066:Palatine Tonsil / Q000166:cytology; D011485:Protein Binding / Q000276:immunology; D012995:Solubility; D000093242:Interleukin-6 Inhibitors
D019013:CD40 Antigens; D023201:CD40 Ligand; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007073:Immunoglobulin E; D007074:Immunoglobulin G; D015850:Interleukin-6; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D000072000:NF-KappaB Inhibitor alpha; D000093242:Interleukin-6 Inhibitors; C000606204:NFKBIA protein, human