Regulation of immunoglobulin gene expression in normal lymphocytes. II. Mechanisms of down-regulation of immunoglobulin secretion after engagement of the B cell antigen receptor.
When B cells are stimulated with lipopolysaccharide (LPS) they start to proliferate and mature into immunoglobulin (Ig)-secreting cells. Co-stimulation with F(ab')2 fragments of antibodies directed against the B cell antigen receptor leads to an inhibition of Ig secretion but not of proliferation. This effect can be mimicked by phorbol esters alone or by a combination of phorbol esters and the Ca2+ ionophore ionomycin, which activate protein kinase C. Here we report that co-stimulation with phorbol esters and ionomycin differentially affects a group of genes normally up-regulated during the course of LPS-dependent B cell activation. Thus, the mRNA coding for the membrane-bound form of IgM and the interleukin 2 receptor (55-kDa protein) continue to be expressed at the levels typical of LPS-stimulated cells, while the mRNA coding for the secreted form of IgM (mu S) and for the J chain are reduced. The loss of mu S mRNA is attributable to an altered processing behavior with respect to the mu precursor and/or a decreased stability of the mRNA itself.
Berberich
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I
Institut für Virologie und Immunobiologie, Universität Würzburg, FRG.
Schimpl
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A
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D005803:Genes, Immunoglobulin; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000235:genetics
D007144:Immunoglobulin J-Chains; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D010703:Phorbol Esters; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D015375:Receptors, Interleukin-2; D015759:Ionomycin