Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Studies on B Cell Precursors

Fine characterization of childhood and adult acute lymphoblastic leukemia (ALL) by a proB and preB surrogate light chain-specific mAb and a proposal for a new B cell ALL classification

Leukemia volume 14, pages 2103–2111 (2000)Cite this article

Abstract

The expression of the surrogate light chain (ΨL) – made of the λ-like (or λ5) and the VpreB proteins – is a B cell-specific maturation marker. Using an anti-human VpreB mAb (4G7), we recently identified in human normal bone marrows, proB and preB cells that express the ΨH–ΨL proB (proBCR) and the μ-ΨL preB (preBCR) receptors, respectively. In the present study, FACS and biochemical analysis confirm the broad proB and preB reactivity of the 4G7 mAb that contrasts with the narrow specificity of other available anti-ΨL reagents for preB cells. This mAb was used to explore intracytoplasmic and cell surface expression of the VpreB protein on a series of 92 precursor B cell ALLs (from 40 child and 52 adult patients), in combination with 24 other mAbs. The major result concerns the identification within proB (or BI) and common (or BII) ALLs, of proBCR− and proBCR+ ALLs that express the VpreB in the cytoplasm or at the cell surface, respectively. The percentage of ALLs within these two VpreB sub-groups differ considerably between the ALL origin. In the pediatric series, ALLs present in the majority a proBCR+ phenotype whereas we observed a proBCR− phenotype for adult ALLs. Based on VpreB expression, and in combination with other published data, we propose a refined classification for precursor B cell ALLs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Kitamura D, Kudo A, Schaal S, Müller W, Melchers F, Rajewsky K . A critical role of lambda5 protein in B cell development Cell 1992 69: 823–831

    Article  CAS  Google Scholar 

  2. Lam KP, Kuhn R, Rajewsky K . In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death (see comments) Cell 1997 90: 1073–1083

    Article  CAS  Google Scholar 

  3. Pelanda R, Schwers S, Sonoda E, Torres RM, Nemazee D, Rajewsky K . Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification Immunity 1997 7: 765–775

    Article  CAS  Google Scholar 

  4. Kerr WG, Cooper MD, Feng L, Burrows PD, Hendershot LM . μ heavy chains can associate with a pseudo light chain complex (ΨL) in human pre-B cell lines Int Immunol 1989 1: 355–361

    Article  CAS  Google Scholar 

  5. Schiff C, Milili M, Bossy D, Tabilio A, Falzetti F, Gabert J, Mannoni P, Fougereau M . lambda-Like and V pre-B genes expression: an early B-lineage marker of human leukemias Blood 1991 78: 1516–1525

    Article  CAS  Google Scholar 

  6. Sakaguchi N, Melchers F . λ5, a new light chain related locus selectively expressed in pre-B lymphocytes Nature 1986 324: 579–582

    Article  CAS  Google Scholar 

  7. Kudo A, Sakaguchi N, Melchers F . Organization of the murine Ig-related λ5 gene transcribed selectively in pre-B lymphocytes EMBO J 1987 6: 103–107

    Article  CAS  Google Scholar 

  8. Bauer SR, Kudo A, Melchers F . Structure and preB lymphocyte restricted expression of the VpreB gene in humans and conservation of its structure in other mammalian species EMBO J 1988 7: 111–116

    Article  CAS  Google Scholar 

  9. Ye J, McCray SK, Clarke SH . The transition of pre-BI to pre-BII cells is dependent on the VH structure of the μ/surrogate L chain receptor EMBO J 1996 15: 1524–1533

    Article  CAS  Google Scholar 

  10. Milili M, Schiff C, Fougereau M, Tonnelle C . The VDJ repertoire expressed in human preB cells reflects the selection of bona fide heavy chains Eur J Immunol 1996 26: 63–69

    Article  CAS  Google Scholar 

  11. ten Boekel E, Melchers F, Rolink AG . Changes in the V(H) gene repertoire of developing precursor B lymphocytes in mouse bone marrow mediated by the pre-B cell receptor Immunity 1997 7: 357–368

    Article  CAS  Google Scholar 

  12. Löffert D, Ehlich A, Müller W, Rajewsky K . Surrogate light chain expression is required to establish immunoglobulin heavy chain allelic exclusion during early B cell development Immunity 1996 4: 133–144

    Article  Google Scholar 

  13. Bossy D, Salamero J, Olive D, Fougereau M, Schiff C . Structure, biosynthesis and transduction properties of the human μ-ΨL complex: similar behavior of preB and intermediate preB-B cells in transducing ability Int Immunol 1993 5: 467–478

    Article  CAS  Google Scholar 

  14. Kuwahara K, Kawai T, Mitsuyoshi S, Matsuo Y, Kikuchi H, Imajoh-Ohmi S, Hashimoto E, Inui S, Cooper MD, Sakaguchi N . Cross-linking of B cell antigen receptor-related structure of pre-B cell lines induces tyrosine phosphorylation of p85 and p110 subunits and activation of phosphatidylinositol 3-kinase Int Immunol 1996 8: 1273–1285

    Article  CAS  Google Scholar 

  15. Lassoued K, Nunez CA, Billips L, Kubagawa H, Monteiro RC, LeBien TW, Cooper MD . Expression of surrogate light chain receptors is restricted to a late stage in pre-B cell differentiation Cell 1993 73: 73–86

    Article  CAS  Google Scholar 

  16. Lassoued K, Illges H, Benlagha K, Cooper MD . Fate of surrogate light chains in B lineage cells J Exp Med 1996 183: 421–429

    Article  CAS  Google Scholar 

  17. Meffre E, Fougereau M, Argenson JN, Aubaniac JM, Schiff C . Cell surface expression of surrogate light chain (ΨL) in the absence of μ on human pro-B cell lines and normal pro-B cells Eur J Immunol 1996 26: 2172–2180

    Article  CAS  Google Scholar 

  18. Sanz E, De La Hera A . A novel anti-Vpre-B antibody identifies immunoglobulin-suprogate receptors on the surface of human pro-B cells J Exp Med 1996 183: 2693–2698

    Article  CAS  Google Scholar 

  19. Ghia P, ten Boekel E, Sanz E, De La Hera A, Rolink A, Melchers F . 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 J Exp Med 1996 184: 2217–2229

    Article  CAS  Google Scholar 

  20. Lemmers B, Gauthier L, Guelpa-Fonlupt V, Fougereau M, Schiff C . The human (PsiL+mu−) proB complex: cell surface expression and biochemical structure of a putative transducing receptor Blood 1999 93: 4336–4346

    Article  CAS  Google Scholar 

  21. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C . Proposals for the classification of the acute leukaemias. French–American–British (FAB) co-operative group Br J Haematol 1976 33: 451–458

    Article  CAS  Google Scholar 

  22. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C . The morphological classification of acute lymphoblastic leukaemia: concordance among observers and clinical correlations Br J Haematol 1981 47: 553–561

    Article  CAS  Google Scholar 

  23. Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van't Veer MB . Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL) Leukemia 1995 9: 1783–1786

    CAS  PubMed  Google Scholar 

  24. Tsuganezawa K, Kiyokawa N, Matsuo Y, Kitamura F, Toyama-Sorimachi N, Kuida K, Fujimoto J, Karasuyama H . 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 1998 92: 4317–4324

    Article  CAS  Google Scholar 

  25. Stong RC, Korsmeyer SJ, Parkin JL, Arthur DC, Kersey JH . Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics Blood 1985 65: 21–31

    Article  CAS  Google Scholar 

  26. Hurwitz R, Hozier J, LeBien T, Minowada J, Gajl-Peczalska K, Kubonishi I, Kersey J . Characterization of a leukemic cell line of the pre-B phenotype Int J Cancer 1979 23: 174–180

    Article  CAS  Google Scholar 

  27. Gauthier L, Lemmers B, Guelpa-Fonlupt V, Fougereau M, Schiff C . Mu-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 1999 162: 41–50

    CAS  PubMed  Google Scholar 

  28. Baruchel A, Leverger G, Schaison G . Use of immunophenotype as part of the prognostic stratification for childhood ALL in the FRALLE 93 protocol Leuk Lymphoma 1994 13: (Suppl. 1) 91–93

    Article  Google Scholar 

  29. Boucheix C, David B, Sebban C, Racadot E, Bene MC, Bernard A, Campos L, Jouault H, Sigaux F, Lepage E . Immunophenotype of adult acute lymphoblastic leukemia, clinical parameters, and outcome: an analysis of a prospective trial including 562 tested patients (LALA87). French Group on Therapy for Adult Acute Lymphoblastic Leukemia Blood 1994 84: 1603–1612

    Article  CAS  Google Scholar 

  30. Willman CL . Flow Cytometric Analysis of Hematologic Specimen. Neoplastic Hematology Willams & Wilkins: Baltimore 1992 pp 169–195

  31. Biondi A, Rambaldi A, Rossi V, Elia L, Caslini C, Basso G, Battista R, Barbui T, Mandelli F, Masera G . Detection of ALL-1/AF4 fusion transcript by reverse transcription-polymerase chain reaction for diagnosis and monitoring of acute leukemias with the t(4;11) translocation Blood 1993 82: 2943–2947

    Article  CAS  Google Scholar 

  32. Raynaud S, Mauvieux L, Cayuela JM, Bastard C, Bilhou-Nabera C, Debuire B, Bories D, Boucheix C, Charrin C, Fiere D, Gabert J . TEL/AML1 fusion gene is a rare event in adult acute lymphoblastic leukemia Leukemia 1996 10: 1529–1530

    CAS  PubMed  Google Scholar 

  33. Hunger SP, Galili N, Carroll AJ, Crist WM, Link MP, Cleary ML . The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias Blood 1991 77: 687–693

    Article  CAS  Google Scholar 

  34. Kawasaki ES, Clark SS, Coyne MY, Smith SD, Champlin R, Witte ON, McCormick FP . Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro Proc Natl Acad Sci USA 1988 85: 5698–5702

    Article  CAS  Google Scholar 

  35. Van Dongen J, Macinctyre E, Gabert J, Delabesse E, Rossi V, Saglio G, Gottardi E, Rambaldi A, Dotti G, Griesinger F, Parreira A, Gameiro P, Diaz MG, Malec M, Langerak AW, San Miguel JF, Biondi A . Standardized RT-PCR analysis of fusion gene transcripts from chromosomal aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia Leukemia 1999 13: 1901–1928

    Article  CAS  Google Scholar 

  36. Costello R, Lafage M, Toiron Y, Brunel V, Sainty D, Arnoulet C, Mozziconacci MJ, Bouabdallah R, Gastaut JA, Maraninchi D . Philadelphia chromosome-negative chronic myeloid leukemia: a report of 14 new cases Br J Haematol 1995 90: 346–352

    Article  CAS  Google Scholar 

  37. Wang YH, Nomura J, Faye-Petersen OM, Cooper MD . Surrogate light chain production during B cell differentiation: differential intracellular versus cell surface expression J Immunol 1998 161: 1132–1139

    CAS  Google Scholar 

  38. Wasserman R, Li YS, Shinton SA, Carmack CE, Manser T, Wiest DL, Hayakawa K, Hardy RR . A novel mechanism for B cell repertoire maturation based on response by B cell precursors to pre-B receptor assembly J Exp Med 1998 187: 259–264

    Article  CAS  Google Scholar 

  39. ten Boekel E, Melchers F, Rolink AG . Precursor B cells showing H chain allelic inclusion display allelic exclusion at the level of pre-B cell receptor surface expression Immunity 1998 8: 199–207

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank D Blaise, R Bouhabdalla and G Michel for referring patients and M-J Mozziconacci, M Lafage-Pochitaloff and A-M Vagner-Capodano for the ALL karyotyping. For excellent technical assistance we are indebted to Y Toiron (RT-PCR analysis) and to F Baudoin, D Jayme and N Geoffroy (immunophenotyping). We also thank V-J Bardou for the statistical analysis, M Fougereau and J Ewbank for critical reading of the manuscript. Anti-human surrogate light chain mAbs (HSL96, 11 and 2) were kindly provided by H Karasuyama. This work was supported by CNRS (Centre National de la Recherche Scientifique), INSERM (Institut National de la Santé et de la Recherche Médicale), ARC (Association de Recherche contre le Cancer, grant No 6345), La Ligue contre le Cancer (Comité des Bouches du Rhône No. 6027–01 and No. 9592), La Ligue Nationale contre le Cancer and La Fondation de France (Comité Leucémie, No. 99002024).

Author information

Authors and Affiliations

  1. Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France

    B Lemmers & C Schiff

  2. Laboratoire d'Hématologie, Institut Paoli-Calmettes, CHU Timone, Marseille, France

    C Arnoulet, D Sainty & J Gabert

  3. Laboratoire d'Hématologie, CHU Timone, Marseille, France

    C Fossat

  4. Service de Pédiatrie et d'Hématologie Pédiatrique, CHU Timone, Marseille, France

    H Chambost

Authors
  1. B Lemmers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Arnoulet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Fossat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Chambost
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D Sainty
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Gabert
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Schiff
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lemmers, B., Arnoulet, C., Fossat, C. et al. Fine characterization of childhood and adult acute lymphoblastic leukemia (ALL) by a proB and preB surrogate light chain-specific mAb and a proposal for a new B cell ALL classification. Leukemia 14, 2103–2111 (2000). https://doi.org/10.1038/sj.leu.2401932

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2401932

Keywords

This article is cited by

Search

Advanced search

Quick links