title: Egr-1 mRNA expression is independent of regulatory proliferative responses in the immature B cell line WEHI-231.
abstract: We have recently reported cellular growth arrest induced following crosslinking of surface IgM (sIgM) but not surface IgD (sIgD) in the WEHI-231 cell line, representative of the immature B cell stage, and its delta heavy chain (delta) transfectant. An initial report has indicated WEHI-231.7, a subclone of WEHI-231, failed to express Egr-1 mRNA following sIgM crosslinking, in contrast to significant up-regulation found in mature B lymphocytes. The implication for linkage between selective surface immunoglobulin (sIg) signal transduction, expression of immediate/early genes and control of cellular growth imposes an attractive model for induction of immature B cell tolerance. Our investigations examined the relationships between Egr-1 mRNA expression and growth regulation in WEHI-231, WEHI-231.7 and their respective delta-transfectants (WEHI-delta, WEHI-delta 7). We report sIgM and sIgD crosslinking leads to a rapid increase of Egr-1 mRNA expression in WEHI-231 and WEHI-delta but not in the subclone WEHI-231.7 and WEHI-delta 7. Nevertheless, both WEHI-231, WEHI-231.7 and their delta-transfectants demonstrate the ability to induce growth arrest following sIgM but not sIgD crosslinking. Furthermore, we found Egr-1 expression could be achieved by direct activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) circumventing the classical sIg activated phosphatidylinositol signal transduction pathway. Our results suggest Egr-1 expression does not directly participate in growth regulation of immature B cell clones but rather is a consequence of signal transduction through sIg.
authors.affiliation: Mount Sinai Hospital, Department of Medical Genetics and Immunology, University of Toronto, Ontario, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Iwabuchi
authors.forename: D B
authors.initials: DB
authors.lastname: Williams
authors.forename: H P
authors.initials: HP
authors.lastname: Nguyen
authors.forename: N
authors.initials: N
authors.lastname: Hozumi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D007072:Immunoglobulin D / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis*; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate