Effects of anti-immunoglobulin antibodies, interleukin-4 and second messenger agonists on B cells from neonatal mice.
Crosslinking of surface Ig receptors on mature B cells with mitogenic anti-Ig antibodies stimulates phosphoinositide breakdown with subsequent activation of protein kinase C (PKC) and elevation of [Ca2+]i leading to B-cell activation. This response can be mimicked using second messenger agonists such as phorbol 12,13-dibutyrate (PDB) plus a Ca2+ ionophore. Furthermore, interleukin-4 (IL-4) synergizes with sub-mitogenic concentrations of anti-Ig (or with PDB) to activate adult B cells. In contrast anti-Ig does not activate neonatal B cells but rather desensitizes or kills them. The nature of the signals involved in these effects on neonatal B cells is poorly understood. Here we have investigated the proliferative responses of small, resting B cells from 1-, 4-, 8-, and 12-week-old mice stimulated with combinations of anti-Ig, PDB, ionomycin and IL-4. We find that B cells from 8- and 12-week-old mice show an adult pattern of reactivity. B cells from 4-week-old mice respond to high doses of anti-Ig, anti-Ig + IL-4 and also to PDB + ionomycin + IL-4, but not to PDB + ionomycin alone. Neonatal (1-week-old) B cells respond only to the combination of PDB, ionomycin and IL-4. Most strikingly, pre-incubation of neonatal cells with anti-Ig completely abrogates this response, whilst IL-4 renders them refractory to such anti-Ig mediated inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Brines
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RD
Division of Immunology, National Institute for Medical Research, Mill Hill, London, UK.
Klaus
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GG
D000818:Animals; D000831:Animals, Newborn; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D007152:Immunologic Capping; D015847:Interleukin-4 / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA / Q000276:immunology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000187:drug effects / Q000276:immunology; D015290:Second Messenger Systems / Q000187:drug effects*; D013047:Specific Pathogen-Free Organisms
D000888:Antibodies, Anti-Idiotypic; D008222:Lymphokines; D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic; D015847:Interleukin-4; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D011493:Protein Kinase C