E2-2 regulates the expansion of pro-B cells and follicular versus marginal zone decisions.
2006 (English)In: Journal of Immunology, ISSN 0022-1767, Vol. 177, no 10, 6723-6729 p.Article in journal (Refereed) Published
The E-proteins E2A, HeLa E-box binding protein, and E2-2 constitute a class of basic helix-loop-helix transcription factors that differentially affect B cell development. E2A is by far the most investigated and appears to operate at several levels during B cell ontogeny. Less is known concerning the role of the other E-proteins. To address the role of E2-2, we have performed transfers of fetal liver (FL) cells into irradiated Rag-deficient mice. Although the transfer of E2-2-deficient cells alone can reconstitute all B cell subpopulations, albeit with a moderate reduction in cellularity, E2-2-deficient cells have a disadvantage when transferred together with wild-type cells. Cultivation of E2-2(-/-) day 14.5 FL cells on stromal cells and IL-7 revealed a reduced frequency of responding B cell progenitors despite normal IL-7Ralpha surface expression. Real-time PCR analysis revealed that E2-2 mRNA expression is high at the pro-B cell stage and drops sharply at the pre-B cell stage, consistent with a role for E2-2 in pro-B cells. In contrast, E2A mRNA was most abundant in pre-B cells. Analysis of the peripheral repertoire revealed that mice reconstituted with E2-2(-/-) FL cells had an increased proportion of marginal zone (MZ) B cells. Interestingly, E2-2 mRNA was elevated approximately 2-fold (p < 0.01) in follicular compared with MZ B cells. Although E2A mRNA showed a similar tendency, the difference was not significant. Collectively, our findings indicate that E2-2 is required for optimal expansion of pro-B cells, and also influences the follicular vs MZ decision.
Place, publisher, year, edition, pages
2006. Vol. 177, no 10, 6723-6729 p.
Animals, B-Lymphocyte Subsets/*cytology/immunology/metabolism/pathology, Cell Differentiation/genetics/*immunology, Cell Lineage/genetics/immunology, Cell Proliferation, Cells; Cultured, Interleukin-7/physiology, Liver/cytology/embryology/immunology, Mice, Mice; Inbred C57BL, Mice; Knockout, RNA; Messenger/biosynthesis, Spleen/*cytology/*immunology/pathology, Stem Cells/*cytology/immunology/metabolism/pathology, TCF Transcription Factors/biosynthesis/deficiency/*physiology
IdentifiersURN: urn:nbn:se:umu:diva-15303PubMedID: 17082585OAI: oai:DiVA.org:umu-15303DiVA: diva2:154975