IL-10 inhibits lipopolysaccharide-induced murine B cell proliferation and cross-linking of surface antigen receptors or ligation of CD40 restores the response.
The effects of IL-10 on murine B cell proliferation in vitro were investigated. IL-10 inhibited LPS-induced B cell proliferation with an EC50 of approximately 500 pg/ml. IL-10-mediated inhibitory activity was not overtly associated with cytotoxicity or induction of apoptosis. The presence or the absence of T cells and mononuclear phagocytes did not affect the inhibitory activity of IL-10 on LPS-induced proliferation. LPS-stimulated, IL-10-exposed B cells progressed from G0 or from M to G1A of the cell cycle, but were inhibited from entry into subsequent phases. IL-10 had no discernible effect on B cell proliferation elicited with goat anti-mouse IgM plus IL-4. Moreover, cross-linking, but not mere ligation, of surface Ag receptors restored LPS-induced B cell proliferation in the presence of IL-10. The proliferative response to ligation of CD40 with anti-CD40 Abs was also not inhibited by IL-10, and as observed with goat anti-mouse IgM, the presence of such Abs in IL-10-containing B cell cultures allowed for the proliferative response to LPS. A variety of other Abs reactive with murine B cell surface markers were ineffective at modulating the response to IL-10. IL-1, IL-2, IL-4, IL-5, IL-6, IFN-gamma, and TGF-beta were also ineffective in this regard. These observations suggest that IL-10 has a role in the suppression of inappropriate B cell proliferation, i.e., proliferation by B cells that have not effectively interacted with relevant Ag or CD40 ligand.
Marcelletti
J F
JF
LIDAK Pharmaceuticals, La Jolla, CA 92037, USA.
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D002453:Cell Cycle; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000494:pharmacology; D016193:G1 Phase; D007075:Immunoglobulin M / Q000494:pharmacology; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000906:Antibodies; D019013:CD40 Antigens; D003432:Cross-Linking Reagents; D016207:Cytokines; D007075:Immunoglobulin M; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D016753:Interleukin-10; D023201:CD40 Ligand