Differential regulation of mouse B-cell activation by beta-adrenoceptor stimulation depending on type of mitogens.
We investigated the effects of the beta-adrenoceptor agonist isoproterenol (ISO) and the alpha- and beta-adrenoceptor agonist norepinephrine (NE) on murine B-cell activation. Cells were stimulated either by anti-mouse mu-chain antibodies (anti-mu), or by lipopolysaccharide (LPS), or a membrane proteoglycan of Klebsiella pneumoniae (Kp MPG), a T-independent polyclonal activator distinct from LPS, which induces B-cell proliferation and Ig synthesis. ISO and NE enhanced LPS- and Kp MPG-induced B-cell proliferation and maturation into IgM-, IgG- and IgA-secreting cells. The enhancement was prevented by prior addition of the beta-adrenoceptor antagonist propranolol but not by the alpha-adrenoceptor antagonist phentolamine. Earlier events in the LPS- and Kp MPG-stimulated B-cell activation, such as increases in Ia antigen expression and RNA synthesis, were not modified by the catecholamines. Unlike ISO and NE, the membrane-permeant cyclic adenosine 3',5'-monophosphate (cAMP) analogue dibutyryl cAMP (dbcAMP), and the potent adenylate cyclase activator forskolin did not enhance but even inhibited DNA synthesis and Ig secretion stimulated by LPS and Kp MPG. In addition, ISO and NE did not enhance but strongly inhibited anti-mu-induced B-cell proliferation, and these effects were mimicked by dbcAMP and forskolin. Collectively, the data demonstrate that beta-agonists differently modulate B-cell activation depending upon the polyclonal activator, and provide additional evidence for distinct biochemical mechanisms of B-cell activation by anti-mu and LPS. Moreover, our results indicate that beta-adrenergic stimulation up-regulates B-cell responses to LPS and Kp MPG by a novel and cAMP-independent pathway.
Li
Y S
YS
Laboratoire d'Immunologie, INSERM U.80-CNRS URA 1177-UCBL, Lyon, France.
Kouassi
E
E
Revillard
J P
JP
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000276:immunology*; D009638:Norepinephrine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008934:Mitogens; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine