title: IL-4 upregulates Igα and Igβ protein, resulting in augmented IgM maturation and B cell receptor-triggered B cell activation.
abstract: IL-4 is critical for optimal B cell activation and germinal center B cell expansion in T-dependent immune responses; however, the underlying mechanism remains elusive. In the current study, we found that primary B cells express little Igα and Igβ protein despite substantial levels of mRNA. IL-4 markedly upregulates Igα and Igβ protein expression that requires STAT6. Elevated Igα and Igβ protein form heterodimers that associate with IgM and significantly promote IgM maturation and surface IgM expression, resulting in amplified BCR-initiated signaling that is Lyn dependent. In vivo, we found that pregerminal center B cells express upregulated Igα, Igβ, and surface IgM expression, in conjunction with elevated BCR-triggered phosphorylated ERK ex vivo, that are dependent on IL-4 and reversed by in vivo administration of neutralizing anti-IL-4 Ab. Thus, this study elucidates a novel mechanism for cross-talk between the IL-4 and BCRs that programs enhancement of subsequent BCR signaling.
authors.affiliation: Center for Oncology and Cell Biology, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. bguo@nshs.edu
authors.forename: Benchang
authors.initials: B
authors.lastname: Guo
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rothstein
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D051925:CD79 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; D007075:Immunoglobulin M; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases