Modulation of Ig gene expression by Ig binding factors. Suppression of alpha-H chain and lambda-2-L chain mRNA accumulation in MOPC-315 by IgA-binding factor.
Previous reports by a number of laboratories have shown that Ig-binding factors may play a role in the regulation of Ig production by B cells. Although numerous studies have addressed the specificity and biologic function of Ig-binding factors at the cellular level, little information is available regarding the mechanism whereby Ig-binding factor modulates Ig production by B cells at the molecular level. Herein we have examined the specificity and molecular mechanism of the suppression of IgA production mediated by IgA-binding factor. Using the IgA-secreting plasmacytoma, MOPC-315, as a target cell, we have demonstrated that: 1) IgA-binding factor binds to IgA, but not to IgG, IgM, or BSA; 2) IgA-binding factor can suppress proliferation as well as IgA production by MOPC-315; 3) soluble IgA, but not IgG or IgM can inhibit the action of IgA-binding factor; 4) suppression of Ig production by IgA-binding factor is maximal within 8 to 12 h after exposure to the factor and is reversible; 5) IgA-binding factor suppresses IgA production by selectively down-regulating synthesis of IgA H and L chain proteins; 6) IgA-binding factor selectively suppresses transcription of alpha-H chain and lambda-2-L chain genes; 7) IgA-binding factor suppresses accumulation of c-myc mRNA. These findings suggest that IgA-binding factor binds selectively to surface IgA on MOPC-315 and suppresses IgA production by down-regulating transcription of H and L chain genes. Suppression of MOPC-315 proliferation by IgA-binding factor may be related to the concomitant down-regulation of the expression of the c-myc gene. c-myc is deregulated in MOPC-315 by virtue of the reciprocal 15:12 chromosomal translocation present in MOPC-315 where the c-myc gene is translocated and rearranged into the alpha-H chain gene complex. Simultaneous suppression of the expression of c-myc and alpha-H chain genes suggests that these two genes may be coordinately modulated, in plasmacytomas, by IgA-binding factor.
D000818:Animals; D002460:Cell Line; D005260:Female; D005803:Genes, Immunoglobulin; D006131:Growth Inhibitors / Q000502:physiology; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007137:Immunoglobulin alpha-Chains / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D008222:Lymphokines / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010954:Plasmacytoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D029584:Prostatic Secretory Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000032:analysis / Q000502:physiology*
D006131:Growth Inhibitors; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007137:Immunoglobulin alpha-Chains; D007146:Immunoglobulin lambda-Chains; D008222:Lymphokines; D029584:Prostatic Secretory Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013491:Suppressor Factors, Immunologic; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors