Differential regulation of IgA production by TGF-beta and IL-5: TGF-beta induces surface IgA-positive cells bearing IL-5 receptor, whereas IL-5 promotes their survival and maturation into IgA-secreting cells.
Transforming growth factor beta (TGF-beta) and IL-5 have been shown to augment IgA production by LPS-stimulated murine B cells. We investigated the effect of TGF-beta on the expression of surface Ig-isotype and IL-5 receptor on LPS-stimulated B cells. TGF-beta increased the proportion of both surface IgA-positive (sIgA+) B cells and sIgG2b+ B cells and enhanced IgA and IgG2b production by LPS-stimulated B cells. TGF-beta synergized with IL-5 only for IgA production of the seven Ig-isotypes and in combination with IL-5 caused a significant increase in the proportion of sIgA+ B cells up to 17.4%. In contrast, IL-5 decreased the proportion of sIgG2b+ B cells and sIgG3+ B cells and inhibited the production of IgG2b and IgG3 by LPS-stimulated B cells. About 50% of sIgA+ cells induced by TGF-beta expressed IL-5 receptor. They secreted peak levels of IgA and seemed to maintain long viability in the presence of IL-5; whereas TGF-beta had the opposite effects on sIgA+ B cells and down-regulated the IL-5 receptor expression. These results indicate that TGF-beta increases the number of sIgA(+)- and IL-5 receptor-positive B cells which respond to IL-5 giving rise to IgA-secreting cells and also support the notions that TGF-beta preferentially induces switching to sIgA+ B cells and IL-5 induces the maturation of postswitch sIgA+ B cells into IgA-secreting cells in a stepwise fashion.
Sonoda
E
E
Department of Biology, Kumamoto University Medical School, Japan.
Hitoshi
Y
Y
Yamaguchi
N
N
Ishii
T
T
Tominaga
A
A
Araki
S
S
Takatsu
K
K
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007134:Immunoglobulin Switch Region / Q000187:drug effects; D015848:Interleukin-5 / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000032:analysis / Q000187:drug effects; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D013154:Spleen / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000906:Antibodies; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007132:Immunoglobulin Isotypes; D015848:Interleukin-5; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D016212:Transforming Growth Factor beta