Cytokine-induced differentiation of IgA B cells: studies using an IgA expressing B-cell lymphoma.
Cytokines such as interleukin-5 (IL-5) and transforming growth factor beta 1 (TGF beta 1) increase IgA production by heterogeneous populations of lipopolysaccharide (LPS)-activated murine B cells. We have used IgA expressing murine B-lymphoma cells CH12.LX.C4.4F10 (4F10) to define the activity of these and other cytokines on IgA secretion at the single-cell level, membrane IgA expression, IgA polymerization and cell growth. IL-5 as well as LPS significantly increases IgA secretion of 4F10 cells, whereas TGF beta 1, a cytokine known to stimulate isotype switching to IgA among surface IgM-bearing B cells, inhibits IgA secretion. When tested alone, IL-1 beta, IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) do not significantly alter IgA secretion. However, there is a synergistic increase in IgA secretion when 4F10 cells are co-stimulated with IL-5 and IL-4, while IFN-gamma inhibits IL-5-stimulated up-regulation of IgA secretion. In parallel with increased IgA secretion after cytokine stimulation, 4F10 cells display less membrane IgA. Increased J-chain steady-state mRNA levels after IL-5 or LPS stimulation are paralleled by increased mRNA levels for secreted IgA, but are not accompanied by alterations in the ratio of monomeric to polymeric IgA. IL-5 and LPS initially stimulated but later inhibited 4F10 cell proliferation suggesting an inverse relationship between proliferation and differentiation in this cell line. 4F10 cells are a useful model for the characterization of discrete aspects of IgA B-cell differentiation, since the secretory and membrane Ig and proliferative responses of this IgA B-cell line to cytokines and LPS appear to parallel those of freshly isolated murine B cells.
Eckmann
L
L
Department of Medicine, University of California, San Diego, La Jolla 92093-0623.
Morzycka-Wroblewska
E
E
Smith
J R
JR
Kagnoff
M F
MF
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology; D051379:Mice; D016212:Transforming Growth Factor beta / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000912:Antibodies, Neoplasm; D016207:Cytokines; D007070:Immunoglobulin A; D015848:Interleukin-5; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta