J. Exp. Med.
© The Rockefeller University Press
0022-1007/96/12/2217/14 $2.00
Volume 184 December 1996 2217-2230

Ordering of Human Bone Marrow B Lymphocyte Precursors by Single-Cell Polymerase Chain Reaction Analyses of the Rearrangement Status of the Immunoglobulin H and L Chain Gene Loci

By Paolo Ghia,^* Edwin ten Boekel,^* Eva Sanz,^§ Antonio de la Hera,^§ Antonius Rolink,^* and Fritz Melchers^*

From the ^* Basel Institute for Immunology, CH-4005 Basel, Switzerland;  Centro de Investigaciones Biologicas, E-28006 Madrid, Spain; and ^§ Department of Medicine, Alcala University, E-28871 Madrid, Spain

CD19⁺CD10⁺ human B lineage bone marrow cells were separated into cycling or resting cells, which differ in their expression of CD34, V_preB, recombination activating gene (RAG-1), and terminal deoxynucleotidyl transferase (TdT). Polymerase chain reaction analyses developed for D_HJ_H and VJ, VJK^(de) and VK^(de) rearrangements with DNA of single cells and a comparison with B lineage cell development in mouse bone marrow, allow to delineate the human B lymphocyte pathway of development as follows: CD34⁺V_preB⁺RAG-1⁺TdT⁺, D_HJ_H-rearranged, L germline cycling pre-B I cells  CD34V_preB⁺µH chain⁺ (pre-B receptor⁺) RAG-1TdT, V_HD_HJ_H-rearranged, L germline, cycling pre-B II cells  CD34V_preB, intracytoplasmic µH chain⁺ (pre-B receptor) RAG-1^+/ TdT, V_HD_HJ_H-rearranged, mainly L germline cycling pre-B II cells  CD34V_preB intracytoplasmic µH chain⁺, RAG-1⁺TdT, V_HD_HJ_H-rearranged, VJ-rearranged, IgM, resting pre-B II cells CD34⁺V_preB, sIgM⁺, RAG-1⁺TdT, V_HD_HJ_H- and VJ-rearranged IgM⁺ immature B cells  CD34, CD10, sIgM⁺/sIgD⁺ mature B cells. This order, for the first time established for human B lineage cells, shows striking similarities with that established for mouse B lineage cells in bone marrow.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Hoffmann, R., Lottaz, C., Kuhne, T., Rolink, A., Melchers, F. (2007). Neutrality, Compensation, and Negative Selection during Evolution of B-Cell Development Transcriptomes. Mol Biol Evol 24: 2610-2618 [Abstract] [Full Text]  
• Leandro, M. J., Cooper, N., Cambridge, G., Ehrenstein, M. R., Edwards, J. C. W. (2007). Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy. Rheumatology (Oxford) 46: 29-36 [Abstract] [Full Text]  
• van Zelm, M. C., van der Burg, M., de Ridder, D., Barendregt, B. H., de Haas, E. F. E., Reinders, M. J. T., Lankester, A. C., Revesz, T., Staal, F. J. T., van Dongen, J. J. M. (2005). Ig Gene Rearrangement Steps Are Initiated in Early Human Precursor B Cell Subsets and Correlate with Specific Transcription Factor Expression. J. Immunol. 175: 5912-5922 [Abstract] [Full Text]  
• Imamura, R., Miyamoto, T., Yoshimoto, G., Kamezaki, K., Ishikawa, F., Henzan, H., Kato, K., Takase, K., Numata, A., Nagafuji, K., Okamura, T., Sata, M., Harada, M., Inaba, S. (2005). Mobilization of Human Lymphoid Progenitors after Treatment with Granulocyte Colony-Stimulating Factor. J. Immunol. 175: 2647-2654 [Abstract] [Full Text]  
• Samuels, J., Ng, Y.-S., Coupillaud, C., Paget, D., Meffre, E. (2005). Impaired early B cell tolerance in patients with rheumatoid arthritis. JEM 201: 1659-1667 [Abstract] [Full Text]  
• Langerak, A. W., Nadel, B., de Torbal, A., Wolvers-Tettero, I. L. M., van Gastel-Mol, E. J., Verhaaf, B., Jager, U., van Dongen, J. J. M. (2004). Unraveling the Consecutive Recombination Events in the Human IGK Locus. J. Immunol. 173: 3878-3888 [Abstract] [Full Text]  
• Thai, T.-H., Kearney, J. F. (2004). Distinct and Opposite Activities of Human Terminal Deoxynucleotidyltransferase Splice Variants. J. Immunol. 173: 4009-4019 [Abstract] [Full Text]  
• Smith, E., Sigvardsson, M. (2004). The roles of transcription factors in B lymphocyte commitment, development, and transformation. J. Leukoc. Biol. 75: 973-981 [Abstract] [Full Text]  
• Magrangeas, F., Cormier, M.-L., Descamps, G., Gouy, N., Lode, L., Mellerin, M.-P., Harousseau, J.-L., Bataille, R., Minvielle, S., Avet-Loiseau, H. (2004). Light-chain only multiple myeloma is due to the absence of functional (productive) rearrangement of the IgH gene at the DNA level. Blood 103: 3869-3875 [Abstract] [Full Text]  
• Ghia, P., Prato, G., Scielzo, C., Stella, S., Geuna, M., Guida, G., Caligaris-Cappio, F. (2004). Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly. Blood 103: 2337-2342 [Abstract] [Full Text]  
• Jasper, P. J., Zhai, S.-K., Kalis, S. L., Kingzette, M., Knight, K. L. (2003). B Lymphocyte Development in Rabbit: Progenitor B Cells and Waning of B Lymphopoiesis. J. Immunol. 171: 6372-6380 [Abstract] [Full Text]  
• Reynaud, D., Lefort, N., Manie, E., Coulombel, L., Levy, Y. (2003). In vitro identification of human pro-B cells that give rise to macrophages, natural killer cells, and T cells. Blood 101: 4313-4321 [Abstract] [Full Text]  
• Sanz, E., Alvarez-Mon, M., Martinez-A, C., de la Hera, A. (2003). Human cord blood CD34+Pax-5+ B-cell progenitors: single-cell analyses of their gene expression profiles. Blood 101: 3424-3430 [Abstract] [Full Text]  
• Sinkora, M., Sun, J., Sinkorova, J., Christenson, R. K., Ford, S. P., Butler, J. E. (2003). Antibody Repertoire Development in Fetal and Neonatal Piglets. VI. B Cell Lymphogenesis Occurs at Multiple Sites with Differences in the Frequency of In-frame Rearrangements. J. Immunol. 170: 1781-1788 [Abstract] [Full Text]  
• Rossi, M. I. D., Yokota, T., Medina, K. L., Garrett, K. P., Comp, P. C., Schipul, A. H. Jr, Kincade, P. W. (2003). B lymphopoiesis is active throughout human life, but there are developmental age-related changes. Blood 101: 576-584 [Abstract] [Full Text]  
• Gauthier, L., Rossi, B., Roux, F., Termine, E., Schiff, C. (2002). Galectin-1 is a stromal cell ligand of the pre-B cell receptor (BCR) implicated in synapse formation between pre-B and stromal cells and in pre-BCR triggering. Proc. Natl. Acad. Sci. USA 99: 13014-13019 [Abstract] [Full Text]  
• Gisler, R., Sigvardsson, M. (2002). The Human V-PreB Promoter Is a Target for Coordinated Activation by Early B Cell Factor and E47. J. Immunol. 168: 5130-5138 [Abstract] [Full Text]  
• Fakhari, F. D., Dittmer, D. P. (2002). Charting Latency Transcripts in Kaposi's Sarcoma-Associated Herpesvirus by Whole-Genome Real-Time Quantitative PCR. J. Virol. 76: 6213-6223 [Abstract] [Full Text]  
• Wang, Y.-H., Stephan, R. P., Scheffold, A., Kunkel, D., Karasuyama, H., Radbruch, A., Cooper, M. D. (2002). Differential surrogate light chain expression governs B-cell differentiation. Blood 99: 2459-2467 [Abstract] [Full Text]  
• Bertrand, F. E., Vogtenhuber, C., Shah, N., LeBien, T. W. (2001). Pro-B-cell to pre-B-cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein. Blood 98: 3398-3405 [Abstract] [Full Text]  
• Bjorgan, M. B., Thoen, J. E., Natvig, J. B., Thompson, K. M. (2001). Bm1-Bm5 Classification of Peripheral Blood B Cells Reveals Circulating Germinal Center Founder Cells in Healthy Individuals and Disturbance in the B Cell Subpopulations in Patients with Primary Sjogren's Syndrome. J. Immunol. 167: 3610-3618 [Abstract] [Full Text]  
• Zhao, F., Vilardi, A., Neely, R. J., Choi, J. K. (2001). Promotion of Cell Cycle Progression by Basic Helix-Loop-Helix E2A. Mol. Cell. Biol. 21: 6346-6357 [Abstract] [Full Text]  
• Gisler, R., Jacobsen, S. E. W., Sigvardsson, M. (2000). Cloning of human early B-cell factor and identification of target genes suggest a conserved role in B-cell development in man and mouse. Blood 96: 1457-1464 [Abstract] [Full Text]  
• Szczepanski, T., van 't Veer, M. B., Wolvers-Tettero, I. L. M., Langerak, A. W., van Dongen, J. J. M. (2000). Molecular features responsible for the absence of immunoglobulin heavy chain protein synthesis in an IgH- subgroup of multiple myeloma. Blood 96: 1087-1093 [Abstract] [Full Text]  
• Nomura, K., Kanegane, H., Karasuyama, H., Tsukada, S., Agematsu, K., Murakami, G., Sakazume, S., Sako, M., Tanaka, R., Kuniya, Y., Komeno, T., Ishihara, S., Hayashi, K., Kishimoto, T., Miyawaki, T. (2000). Genetic defect in human X-linked agammaglobulinemia impedes a maturational evolution of pro-B cells into a later stage of pre-B cells in the B-cell differentiation pathway. Blood 96: 610-617 [Abstract] [Full Text]  
• LeBien, T. W. (2000). Fates of human B-cell precursors. Blood 96: 9-23 [Abstract] [Full Text]  
• Ogawa, M., Boekel, E. t., Melchers, F. (2000). Identification of CD19-B220+c-Kit+Flt3/Flk-2+cells as early B lymphoid precursors before pre-B-I cells in juvenile mouse bone marrow. Int Immunol 12: 313-324 [Abstract] [Full Text]  
• Gustincich, S., Feigenspan, A., Sieghart, W., Raviola, E. (1999). Composition of the GABAA Receptors of Retinal Dopaminergic Neurons. J. Neurosci. 19: 7812-7822 [Abstract] [Full Text]  
• Rao, S. P., Riggs, J. M., Friedman, D. F., Scully, M. S., LeBien, T. W., Silberstein, L. E. (1999). Biased VH Gene Usage in Early Lineage Human B Cells: Evidence for Preferential Ig Gene Rearrangement in the Absence of Selection. J. Immunol. 163: 2732-2740 [Abstract] [Full Text]  
• Pongers-Willemse, M. J., Langerak, A. W., Harts, W. A., Wijkhuijs, A. J.M., van Wering, E. R., van Dongen, J. J.M. (1999). Ig Heavy Chain Gene Rearrangements in T-Cell Acute Lymphoblastic Leukemia Exhibit Predominant DH6-19 and DH7-27 Gene Usage, Can Result in Complete V-D-J Rearrangements, and Are Rare in T-Cell Receptor alpha beta Lineage. Blood 93: 4079-4085 [Abstract] [Full Text]  
• Lemmers, B., Gauthier, L., Guelpa-Fonlupt, V., Fougereau, M., Schiff, C. (1999). The Human (Psi L+µ-) proB Complex: Cell Surface Expression and Biochemical Structure of a Putative Transducing Receptor. Blood 93: 4336-4346 [Abstract] [Full Text]  
• Gauthier, L., Lemmers, B., Guelpa-Fonlupt, V., Fougereau, M., Schiff, C. (1999). {micro}-Surrogate Light Chain Physicochemical Interactions of the Human PreB Cell Receptor: Implications for VH Repertoire Selection and Cell Signaling at the PreB Cell Stage. J. Immunol. 162: 41-50 [Abstract] [Full Text]  
• Fluckiger, A.-C., Sanz, E., Garcia-Lloret, M., Su, T., Hao, Q.-L., Kato, R., Quan, S., de la Hera, A., Crooks, G. M., Witte, O. N., Rawlings, D. J. (1998). In Vitro Reconstitution of Human B-Cell Ontogeny: From CD34+ Multipotent Progenitors to Ig-Secreting Cells. Blood 92: 4509-4520 [Abstract] [Full Text]  
• Tsuganezawa, K., Kiyokawa, N., Matsuo, Y., Kitamura, F., Toyama-Sorimachi, N., Kuida, K., Fujimoto, J., Karasuyama, H. (1998). Flow Cytometric Diagnosis of the Cell Lineage and Developmental Stage of Acute Lymphoblastic Leukemia by Novel Monoclonal Antibodies Specific to Human Pre-B-Cell Receptor. Blood 92: 4317-4324 [Abstract] [Full Text]  
• Dworzak, M. N., Fritsch, G., Froschl, G., Printz, D., Gadner, H. (1998). Four-Color Flow Cytometric Investigation of Terminal Deoxynucleotidyl Transferase-Positive Lymphoid Precursors in Pediatric Bone Marrow: CD79a Expression Precedes CD19 in Early B-Cell Ontogeny. Blood 92: 3203-3209 [Abstract] [Full Text]  
• Trigueros, C., Ramiro, A. R., Carrasco, Y. R., de Yebenes, V. G., Albar, J. P., Toribio, M. L. (1998). Identification of a Late Stage of Small Noncycling pTalpha -  Pre-T Cells as Immediate Precursors of T Cell Receptor alpha /beta +  Thymocytes. JEM 188: 1401-1412 [Abstract] [Full Text]  
• Meffre, E., Papavasiliou, F., Cohen, P., de Bouteiller, O., Bell, D., Karasuyama, H., Schiff, C., Banchereau, J., Liu, Y.-J., Nussenzweig, M. C. (1998). Antigen Receptor Engagement Turns off the V(D)J Recombination Machinery in Human Tonsil B Cells. JEM 188: 765-772 [Abstract] [Full Text]  
• Wang, Y.-H., Nomura, J., Faye-Petersen, O. M., Cooper, M. D. (1998). Surrogate Light Chain Production During B Cell Differentiation: Differential Intracellular Versus Cell Surface Expression. J. Immunol. 161: 1132-1139 [Abstract] [Full Text]  
• Wang, H., Diamond, R. A., Rothenberg, E. V. (1998). Cross-lineage expression of Ig-beta (B29) in thymocytes: Positive and negative gene regulation to establish T cell identity. Proc. Natl. Acad. Sci. USA 95: 6831-6836 [Abstract] [Full Text]  
• Petrovic, A. S., Young, R. L., Hilgarth, B., Ambros, P., Korsmeyer, S. J., Jaeger, U. (1998). The Ig Heavy Chain 3' End Confers a Posttranscriptional Processing Advantage to Bcl-2-IgH Fusion RNA in t(14;18) Lymphoma. Blood 91: 3952-3961 [Abstract] [Full Text]  
• Ghia, P., Boussiotis, V. A., Schultze, J. L., Cardoso, A. A., Dorfman, D. M., Gribben, J. G., Freedman, A. S., Nadler, L. M. (1998). Unbalanced Expression of Bcl-2 Family Proteins in Follicular Lymphoma: Contribution of CD40 Signaling in Promoting Survival. Blood 91: 244-251 [Abstract] [Full Text]  
• Davi, F., Faili, A., Gritti, C., Blanc, C., Laurent, C., Sutton, L., Schmitt, C., Merle-Beral, H. (1997). Early Onset of Immunoglobulin Heavy Chain Gene Rearrangements in Normal Human Bone Marrow CD34+ Cells. Blood 90: 4014-4021 [Abstract] [Full Text]  
• Chen, X., Laur, O., Kambayashi, T., Li, S., Bray, R. A., Weber, D. A., Karlsson, L., Jensen, P. E. (2002). Regulated Expression of Human Histocompatibility Leukocyte Antigen (HLA)-DO During Antigen-dependent and Antigen-independent Phases of B Cell Development. JEM 195: 1053-1062 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS