title: Effect of transforming growth factor (TGF)-beta 1 on IgA isotype expression. TGF-beta 1 induces a small increase in sIgA+ B cells regardless of the method of B cell activation.
abstract: Transforming growth factor-beta (TGF-beta) has been reported to play an important role in IgA isotype expression when B cells are stimulated with LPS. The goal of the present study was to determine whether TGF-beta has similar effects on IgA isotype expression under more physiologic conditions utilizing a variety of B cell activation systems. As previously reported, in the LPS system TGF-beta caused a small, but significant, absolute increase in surface IgA (sIgA) expression and a very definite increase in IgA secretion; these effects were enhanced by IL-2 and IL-5. In the case of B cell stimulation with another B cell stimulant, the thymus-independent type II mitogen, anti-IgD-dextran, TGF-beta led to a similar small increase in sIgA expression, but caused suppression of IgA secretion. Using the Th2 cell clones CDC35 and D10 to stimulate resting B cells in a cognate and non-cognate T cell-dependent fashion, respectively, TGF-beta again increased sIgA expression to a similar small extent. TGF-beta at low doses (0.1 ng/ml) did not increase IgA secretion significantly and, at higher doses (1.0 ng/ml) caused significant suppression of IgA secretion. Addition of various cytokines (IL-2, -4, -5, D10sup) other than TGF-beta to stimulated B cells did not increase sIgA expression, but did give rise to increased amounts of IgA secretion, especially when activated D10 T cells were used as the B cell stimulant. Finally, the addition of an antibody against TGF-beta to cultures containing TGF-beta on day 2 led to partial or complete reversal of the inhibitory effects of TGF-beta on IgA secretion. In conclusion, TGF-beta causes a consistent, but small increase in sIgA+ B cells, in cultures of B cells stimulated by a variety of T cell-dependent or independent stimuli. In contrast, TGF-beta either promotes or inhibits B cell survival and IgA secretion, depending on the method of B cell activation. These results are most consistent with the view that TGF-beta provides only a partial or incomplete IgA switch signal but that additional factors are involved in IgA isotype switching and differentiation.
authors.affiliation: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: R O
authors.initials: RO
authors.lastname: Ehrhardt
authors.forename: W
authors.initials: W
authors.lastname: Strober
authors.forename: G R
authors.initials: GR
authors.lastname: Harriman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D007071:Immunoglobulin A, Secretory; D007132:Immunoglobulin Isotypes; D007376:Interleukin-2; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D015847:Interleukin-4