The selection of mature B cells is critically dependent on the expression level of the co-receptor CD19.
CD19 plays a crucial role in mature B cell development as best exemplified by the finding that CD19 deficient mice have severely reduced mature B cell compartments (Engel et al., 1995; Rickert et al., 1995). In the present study we show that the transition into the mature B cell compartments is heavily dependent on the correct amount of CD19 expression. Thus, Nup-98-HoxB4 immortalized hematopoietic stem cells (HSCs) over-expressing CD19 show upon transplantation an impaired pro/pre B to immature B cell transition in the bone marrow, whereas Nup-98-HoxB4 HSCs expressing a shRNA that down-modulates CD19 expression show upon transplantation a strongly reduced mature B cell compartment. Overall our findings indicate that too high CD19 expression might result into too strong BCR signaling in the bone marrow and therefore causing negative selection. Too low CD19 expression might result into too little BCR signaling and thereby preventing the B cells to enter the mature pool (absence of positive selection).
Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Mattenstraße, Basel 284058, Switzerland.
Lilly
L
von Muenchow
Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Mattenstraße, Basel 284058, Switzerland.
Corinne
C
Engdahl
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
Klaus
K
Karjalainen
Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Mattenstraße, Basel 284058, Switzerland. Electronic address: antonius.rolink@unibas.ch.
Antonius G
AG
Rolink
D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics* / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D005786:Gene Expression Regulation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000276:immunology; D054420:Pre-B Cell Receptors / Q000235:genetics* / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
D018941:Antigens, CD19; D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; D028861:Nuclear Pore Complex Proteins; D054420:Pre-B Cell Receptors; D034741:RNA, Small Interfering; D014157:Transcription Factors; C093350:nuclear pore complex protein 98
B cell development; CD19; Nup98–HoxB4; Selection