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.

Abstract

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.

• Authors: S Roman, J S Moore, C Darby, S Müller, R G Hoover
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 140 Issue 10 Pg. 3622-30 (May 15 1988) ISSN: 0022-1767 [Print] United States
• PMID: 3129498 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Growth Inhibitors
• Immunoglobulin A
• Immunoglobulin Heavy Chains
• Immunoglobulin alpha-Chains
• Immunoglobulin lambda-Chains
• Lymphokines
• Prostatic Secretory Proteins
• Proto-Oncogene Proteins
• RNA, Messenger
• RNA, Neoplasm
• Suppressor Factors, Immunologic
• beta-microseminoprotein
• immunoglobulin-binding factors

Topics

• Animals
• Cell Line
• Female
• Genes, Immunoglobulin
• Growth Inhibitors (physiology)
• Immunoglobulin A (biosynthesis, genetics)
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin alpha-Chains (genetics)
• Immunoglobulin lambda-Chains (genetics)
• Lymphokines (analysis, physiology)
• Mice
• Mice, Inbred BALB C
• Plasmacytoma (genetics, immunology, metabolism)
• Prostatic Secretory Proteins
• Proto-Oncogene Proteins (metabolism)
• RNA, Messenger (metabolism)
• RNA, Neoplasm (metabolism)
• Suppressor Factors, Immunologic (analysis, physiology)