Regulation of immunoglobulin gene expression in normal lymphocytes II. Mechanisms of down‐regulation of immunoglobulin secretion after engagement of the B cell antigen receptor

Publisher Website
Google Scholar
Abstract
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 (μs) and for the J chain are reduced. The loss of μS mRNA is attributable to an altered processing behavior with respect to the μ precursor and/or a decreased stability of the mRNA itself.