E2-2 regulates the expansion of pro-B cells and follicular versus marginal zone decisions.
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.
Wikström
Ingela
I
Department of Medical Biosciences, Umeå University, Umeå, Sweden.
Forssell
Johan
J
Goncalves
Mario
M
Colucci
Francesco
F
Holmberg
Dan
D
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015851:Interleukin-7 / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051820:TCF Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D058118:Transcription Factor 7-Like 2 Protein
D015851:Interleukin-7; D012333:RNA, Messenger; D051820:TCF Transcription Factors; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein