Skip to main content
SpringerLink
Log in

Haemopoietic progenitors in the adult mouse omentum: permanent production of B lymphocytes and monocytes

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The coelome-associated lympho-myeloid tissues, including the omentum, are derived from early embryo haemopoietic tissue of the splanchnopleura, and produce B lymphocytes and macrophages. They are reactive in pathologies involving coelomic cavities, in which they can expand in situ the cells of inflammatory infiltrates. We have addressed the question of the role of the adult omentum in permanent basal production of early lymphopoietic progenitors (pro-B/pre-B cells), through characterisation of omentum cells ex vivo, and study of their in vitro differentiation. We have shown that the murine omentum produces early haemopoietic progenitors throughout life, including B-cell progenitors prior to the Ig gene recombination expressing RAG-1 and λ5, as well as macrophages. Their production is stroma-dependent. The omentum stroma can supply in vitro the cytokines (SDF-1α, Flt3 ligand and IL-7) and the molecular environment required for generation of these two cell lineages. Omentum haemopoietic progenitors are similar to those observed in foetal blood cell production, rather than to progenitors found in the adult haemopoietic tissue in the bone marrow—in terms of phenotype expression and differentiation capacity. We conclude that a primitive pattern of haemopoiesis observed in the early embryo is permanently preserved and functional in the adult omentum, providing production of cells engaged in nonspecific protection of abdominal intestinal tissue and of the coelomic cavity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Aiba Y, Ogawa M (1997) Development of natural killer cells, B lymphocytes, macrophages, and mast cells from single haemopoietic progenitors in culture of murine fetal liver cells. Blood 90:3923–3930

    CAS  PubMed  Google Scholar 

  • Akashi K, Traver D, Kondo M, Weissman IL (1999) Lymphoid development from haemopoietic stem cells. Int J Hematol 69:217–226

    CAS  PubMed  Google Scholar 

  • Allman D, Miller JP (2003) Common lymphoid progenitors, early B-lineage precursors, and IL-7: characterizing the trophic and instructive signals underlying early B cell development. Immunol Res 27:131–140

    Article  CAS  PubMed  Google Scholar 

  • Borge OJ, Adolfsson J, Jacobsen AM (1999) Lymphoid-restricted development from multipotent candidate murine stem cells: distinct and complimentary functions of the c-kit and flt3-ligands. Blood 94:3781–3790

    CAS  PubMed  Google Scholar 

  • Collins LS, Dorshkind KA (1987) A stromal cell line from myeloid long-term bone marrow cultures can support myelopoiesis and B lymphopoiesis. J Immunol 138:1082–1087

    CAS  PubMed  Google Scholar 

  • Conley ME (2003) Genes required for B cell development. J Clin Invest 112:1636–1638

    Article  CAS  PubMed  Google Scholar 

  • Cumano A, Paige CJ, Iscove NN, Brady G (1992) Bipotential precursors of B cells and macrophages in murine fetal liver. Nature 356:612–615

    Article  CAS  PubMed  Google Scholar 

  • Cumano A, Dieterlen-Lièvre F, Godin I (1996) Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura. Cell 86:907–916

    Article  CAS  PubMed  Google Scholar 

  • de Andres B, Gonzalo P, Minguet S, Martinez-Marin JA, Soro PG, Marcos MA, Gaspar ML (2002) The first 3 days of B-cell development in the mouse embryo. Blood 100:4074–4081

    Article  PubMed  Google Scholar 

  • Douagi I, Vieira P, Cumano A (2002) Lymphocyte commitment during embryonic development, in the mouse. Semin Immunol 14:361–369

    Article  PubMed  Google Scholar 

  • Egawa T, Kawabata K, Kawamoto H, Amada K, Okamoto R, Fujii N, Kishimoto T, Katsura Y, Nagasawa T (2001) The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor. Immunity 15:323–334

    Article  CAS  PubMed  Google Scholar 

  • Godin I, Dieterlen-Lièvre F, Cumano A (1995) Emergence of multipotent hemopoietic cells in the yolk sac and para-aortic splanchnopleura in mouse embryos, beginning at 8.5 days post coitus. Proc Natl Acad Sci U S A 92:773–777

    CAS  PubMed  Google Scholar 

  • Godin I, Garcia-Porrero JA, Dieterlen-Lièvre F, Cumano A (1999) Stem cell emergence and hemopoietic activity are incompatible in mouse intraembryonic sites. J Exp Med 190:43–52

    Article  CAS  PubMed  Google Scholar 

  • Hardy RR, Hayakawa K (1994) CD5 B cells, a fetal B cell lineage. Adv Immunol 55:297–339

    CAS  PubMed  Google Scholar 

  • Haughton G, Arnold LW, Whitmore AC, Clarke SH (1993) B1 cells are made, not born. Immunol Today 14:84–87

    Article  CAS  PubMed  Google Scholar 

  • Hayakawa K, Hardy RR, Herzenberg LA, Herzenberg LA (1985) Progenitors for Ly-1 B cells are distinct from progenitors for other B cells. J Exp Med 161:1554–1568

    Article  CAS  PubMed  Google Scholar 

  • Hayakawa K, Asano M, Shinton SA, Gui M, Wen LJ, Dashoff J, Hardy RR (2003) Positive selection of anti-thy-1 autoreactive B-1 cells and natural serum antibody production independent from bone marrow B cell development. J Exp Med 197:87–99

    Article  CAS  PubMed  Google Scholar 

  • Heyworth CM, Spooncer E (1993) In vitro clonal assays for murine multipotential and lineage restricted myeloid cells. In: Testa NG, Molineux G (eds) Haemopoiesis: a pratical approach. Oxford University Press, Oxford, p 37

    Google Scholar 

  • Hsu LY, Lauring J, Liang HE, Greenbaum S, Cado D, Zhuang Y, Schlissel MS (2003) A conserved transcriptional enhancer regulates RAG gene expression in developing B cells. Immunity 19:105–117

    Article  CAS  PubMed  Google Scholar 

  • Kee BL, Cumano A, Iscove NN, Paige CJ (1994) Stromal cell independent growth of bipotent B cell-macrophage precursors from murine fetal liver. Int Immunol 6:401–407

    CAS  PubMed  Google Scholar 

  • Kondo M, Weissman IL, Akashi K (1997) Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91:661–672

    Article  CAS  PubMed  Google Scholar 

  • Kubai L, Auerbach R (1999) A new source of embryonic lymphocytes in the mouse. Nature 301:154–156

    Google Scholar 

  • Kuwata N, Igarashi H, Ohmura T, Aizawa A, Sakaguchi N (1999) Cutting edge: absence of expression of RAG1 in peritoneal B-1 cells detected by knocking into RAG1 locus with green fluorescent protein gene. J Immunol 163:6355–6359

    CAS  PubMed  Google Scholar 

  • Lacaud G, Carlsson L, Keller G (1998) Identification of a fetal haemopoietic precursors with B cell, T cell, and macrophage potential. Immunity 9:827–838

    Article  CAS  PubMed  Google Scholar 

  • Lenzi HL, Oliveira DN, Pelajo-Machado M, Borojevic R, Lenzi JA (1996) Coelome-associated lymphomyeloid tissue (milky spots): site of lymphoid and myelomonocytic cell generation. Braz J Med Biol Res 29:19–24

    CAS  PubMed  Google Scholar 

  • Li YS, Wasserman R, Hayakawa K, Hardy RR (1996) Identification of the earliest B lineage stage in mouse bone marrow. Immunity 5:527–535

    Article  CAS  PubMed  Google Scholar 

  • Lu LS, Tung J, Baumgarth N, Herman O, Gleimer M, Herzenberg LA, Herzenberg LA (2000) Identification of a germ-line pro-B cell subset that distinguishes the fetal/neonatal from the adult B cell development pathway. Proc Natl Acad Sci USA 99:3007–3012

    Article  Google Scholar 

  • Lu M, Kawamoto H, Katsube Y, Ikawa T, Katsura Y (2002) The common myelolymphoid progenitor: a key intermediate stage in hemopoiesis generating T and B cells. J Immunol 169:3519–3525

    CAS  PubMed  Google Scholar 

  • Macpherson AJS, Lamarre A, McCoy K, Harriman GR, Odermatt B, Dougan G, Hengartner H, Zinkernagel RM (2001) IgA production without μ or δ chain expression in developing B cells. Nat Immunol 2:625–631

    Article  CAS  PubMed  Google Scholar 

  • Marcos MA, Huetz F, Pereira P, Andreu JL, Martinez CA, Coutinho A (1989) Further evidence for coelomic-associated B lymphocytes. Eur J Immunol 19:2031–2035

    CAS  PubMed  Google Scholar 

  • Marcos MA, Morales-Alcelay S, Godin I, Dieterlen-Lièvre F, Copin SG, Gaspar ML (1997) Antigenic phenotype and gene expression pattern of lymphohaemopoietic progenitors during early mouse ontogeny. J Immunol 158:2627–2637

    CAS  PubMed  Google Scholar 

  • Martin F, Kearney JF (2001) B-1 cells: similarities and differences with other B cell subsets. Curr Opin Immunol 13:195–201

    Article  CAS  PubMed  Google Scholar 

  • Mebius RE, Miyamoto T, Christensen J, Domen J, Cupedo T, Weissman IL, Akashi K (2001) The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+ CD4+ CD3− cells, as well as macrophages. J Immunol 166:6593–6601

    CAS  PubMed  Google Scholar 

  • Morrison SJ, Hemmati HD, Wandycz AM, Weissman IL (1995) The purification and characterization of fetal liver haemopoietic stem cells. Proc Natl Acad Sci U S A 92:10302–10306

    CAS  PubMed  Google Scholar 

  • Morrison SJ, Wandycz AM, Hemmati HD, Wright DE, Weissman IL (1997) Identification of a lineage of multipotent haemopoietic progenitors. Development 124:1929–1939

    CAS  PubMed  Google Scholar 

  • Ogawa M, ten Boekel E, Melchers F (2000) Identification of CD19−B220+c-Kit+Flt3/Flk-2+ cells as early as B lymphoid precursors before pre-B-I cells in juvenile mouse bone marrow. Int Immunol 12:313–324

    Article  CAS  PubMed  Google Scholar 

  • Okubo T, Matsui N, Yanai N, Obinata M (2000) Stroma-dependent maintenance of cytokine responsive haemopoietic progenitor cells derived from long-term bone marrow culture. Cell Struct Funct 25:133–139

    Article  CAS  PubMed  Google Scholar 

  • Petrenko O, Beavis A, Kittappa R, Godin I, Lemischka R (1999) The molecular characterization of the fetal stem cell marker AA4. Immunity 10:691–700

    Article  CAS  PubMed  Google Scholar 

  • Pinho MFB, Hurtado SP, El-Cheikh MC, Rossi MID, Dutra HS, Borojevic R (2002) Myelopoiesis in the omentum of normal mice and during abdominal inflammatory processes. Cell Tissue Res 308:87–96

    Article  CAS  PubMed  Google Scholar 

  • Potter M, Melchers F (2000) Opinions on the nature of B-1 cells and their relationship to B cell neoplasia. Curr Top Microbiol Immunol 252:307–324

    CAS  PubMed  Google Scholar 

  • Rebel VI, Miller CL, Eaves CJ, Lansdorp PM (1996) The repopulation potential of fetal liver haemopoietic stem cells in mice exceeds that of their adult bone marrow counterparts. Blood 87:3500–3507

    CAS  PubMed  Google Scholar 

  • Sagara S, Sugaya K, Tokoro Y, Tanaka S, Takano H, Kodama H, Nakauchi H, Takahama Y (1997) B220 expression by T lymphoid progenitors cells in mouse fetal liver. J Immunol 158:666–676

    CAS  PubMed  Google Scholar 

  • Sánchez MJ, Holmes A, Miles C, Dzierzak E (1996) Characterization of the first definitive haemopoietic stem cells in the AGM and liver of the mouse embryo. Immunity 5:513–525

    Article  PubMed  Google Scholar 

  • Sitnicka E, Brakebusch C, Martensson IL, Svensson M, Agace WW, Sigvardsson M, Buza-Vidas N, Bryder D, Cilio CM, Ahlenius H, Maraskovsky E, Peschon JJ, Jacobsen SE (2003) Complementary signaling through flt3 and interleukin-7 receptor alpha is indispensable for fetal and adult B cell genesis. J Exp Med 198:1495–1506

    Article  CAS  PubMed  Google Scholar 

  • Solvason N, Kearney J (1989) Reconstitution of lymphocytes subsets in Scid mice by transplantation of fetal primordia. Curr Top Microbiol Immunol 152:161–168

    CAS  PubMed  Google Scholar 

  • Solvason N, Leuhuen A, Kearney JF (1991) An embryonic source of Ly1 but not conventional B cells. Int Immunol 3:543–550

    CAS  PubMed  Google Scholar 

  • Trevisan M, Iscove IN (1995) Phenotype analysis of murine long-term haemopoietic reconstituting cells quantitated competitively in vivo in comparison with more advanced colony-forming progeny. J Exp Med 181:93–103

    Article  CAS  PubMed  Google Scholar 

  • Tudor KSRS, Payne KJ, Yamashita Y, Kincade PW (2000) Functional assessment of precursors from murine bone marrow suggests a sequence of early B lineage differentiation events. Immunity 12:335–345

    Article  CAS  PubMed  Google Scholar 

  • Von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SEG, Murray R (1995) Lymphopenia in interleukin (IL-7) gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med 181:1519–1526

    Article  PubMed  Google Scholar 

  • Wang YH, Stephan RP, Scheffold A, Kunkel D, Karasuyama H, Radbruch A, Cooper MD (2002) Differential surrogate light chain expression governs B cell differentiation. Blood 99:2459–2467

    Article  CAS  PubMed  Google Scholar 

  • Whitlock CA, Robertson D, Witte ON (1984) Murine B cell lymphopoiesis in long term culture. J Immunol Methods 67:353–369

    Article  CAS  PubMed  Google Scholar 

  • Wijffels JFAM, Hendrickx RJBM, Seenbergen JJE, Estermans IL, Beelen RHJ (1992) Milky spots in the mouse omentum may play in important role in the origin of peritoneal macrophages. Res Immunol 143:401–409

    CAS  PubMed  Google Scholar 

  • Yannoutsos N, Wilson P, Yu W, Chen HT, Nussenzweig A, Petrie H, Nussenzweig MC (2001) The role of recombination activating gene (RAG) in induction thymocyte development in vivo. J Exp Med 194:471–480

    Article  CAS  PubMed  Google Scholar 

  • Zhu H, Naito M, Umezu H, Moriyama H, Takatsuka H, Takahashi K, Shultz LD (1997) Macrophage differentiation and expression of macrophage colony-stimulating factor in murine milky spots and omentum after macrophage elimination. J Leukoc Biol 61:436–444

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, and Programa Avançado de Biologia Celular Aplicada à Medicina—Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Maria de Fátima B. Pinho, Sandra P. Hurtado, Márcia C. El-Cheikh & Radovan Borojevic

  2. Departamento de Imunobiologia, Instituto de Biologia, Universidade Federal Fluminense, Niteroi, RJ, Brazil

    Maria de Fátima B. Pinho

  3. Cidade Universitária, Caixa Postal 68021, 21941-970, Rio de Janeiro, Brazil

    Radovan Borojevic

Authors
  1. Maria de Fátima B. Pinho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandra P. Hurtado
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Márcia C. El-Cheikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Radovan Borojevic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Radovan Borojevic.

Additional information

Supported by CNPq, FINEP and PADCT grants of the Brazilian Ministry of Science and Technology, and a FAPERJ grant of the Rio de Janeiro State Government

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pinho, M.B., Hurtado, S.P., El-Cheikh, M.C. et al. Haemopoietic progenitors in the adult mouse omentum: permanent production of B lymphocytes and monocytes. Cell Tissue Res 319, 91–102 (2005). https://doi.org/10.1007/s00441-004-0998-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-004-0998-z

Keywords

Search

Navigation