Summary: Formation of LYMPHOCYTES and PLASMA CELLS from the lymphoid stem cells which develop from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW. These lymphoid stem cells differentiate into T-LYMPHOCYTES; B-LYMPHOCYTES; PLASMA CELLS; or NK-cells (KILLER CELLS, NATURAL) depending on the organ or tissues (LYMPHOID TISSUE) to which they migrate.

Top Publications

  1. Ikawa T, Hirose S, Masuda K, Kakugawa K, Satoh R, Shibano Satoh A, et al. An essential developmental checkpoint for production of the T cell lineage. Science. 2010;329:93-6 pubmed publisher
    ..Our study thus identifies the earliest checkpoint during T cell development and shows that it is Bcl11b-dependent. ..
  2. Schjerven H, McLaughlin J, Arenzana T, Frietze S, Cheng D, Wadsworth S, et al. Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros. Nat Immunol. 2013;14:1073-83 pubmed publisher
    ..Most notably, the two fingers controlled different stages of lymphopoiesis, and finger 4 was selectively required for tumor suppression...
  3. Ichii M, Oritani K, Yokota T, Zhang Q, Garrett K, Kanakura Y, et al. The density of CD10 corresponds to commitment and progression in the human B lymphoid lineage. PLoS ONE. 2010;5:e12954 pubmed publisher
    Requirements for human B lymphopoiesis are still poorly understood, and that has hampered investigation of differentiation events. For example, there are few cell surface antigens that can be used as milestones of lineage progression...
  4. Lu P, Hankel I, Knisz J, Marquardt A, Chiang M, Grosse J, et al. The Justy mutation identifies Gon4-like as a gene that is essential for B lymphopoiesis. J Exp Med. 2010;207:1359-67 pubmed publisher
    A recessive mutation named Justy was found that abolishes B lymphopoiesis but does not impair other major aspects of hematopoiesis...
  5. Ekman A, Ilves M, Iivanainen A. B lymphopoiesis is characterized by pre-B cell marker gene expression in fetal cattle and declines in adults. Dev Comp Immunol. 2012;37:39-49 pubmed publisher
    ..lack of B-lymphoid differentiation in adult bone marrow - OP9 stromal cell co-culture, suggest a decline of B lymphopoiesis in adult cattle...
  6. Awong G, Herer E, Surh C, Dick J, La Motte Mohs R, Zuniga Pflucker J. Characterization in vitro and engraftment potential in vivo of human progenitor T cells generated from hematopoietic stem cells. Blood. 2009;114:972-82 pubmed publisher
    ..Taken together, the identification of T-progenitor subsets readily generated in vitro may offer important avenues to improve cellular-based immune-reconstitution approaches. ..
  7. Parrish Y, Baez I, Milford T, Benitez A, Galloway N, Rogerio J, et al. IL-7 Dependence in human B lymphopoiesis increases during progression of ontogeny from cord blood to bone marrow. J Immunol. 2009;182:4255-66 pubmed publisher
    IL-7 is critical for B cell production in adult mice; however, its role in human B lymphopoiesis is controversial...
  8. Chen M, Logan T, Hochberg M, Shelat S, Yu X, Wilding G, et al. Erythroid dysplasia, megaloblastic anemia, and impaired lymphopoiesis arising from mitochondrial dysfunction. Blood. 2009;114:4045-53 pubmed publisher
    ..macrocytic anemia with abnormal erythroid maturation and megaloblastic changes, as well as profound defects in lymphopoiesis. Mice die of severe fatal anemia at 15 months of age...
  9. Beaudette Zlatanova B, Knight K, Zhang S, Stiff P, Zuniga Pflucker J, Le P. A human thymic epithelial cell culture system for the promotion of lymphopoiesis from hematopoietic stem cells. Exp Hematol. 2011;39:570-9 pubmed publisher
    ..murine Delta-like 1 (TEC-Dl1) for the purpose of establishing a human culture system that supports T lymphopoiesis from hematopoietic progenitor cells (HPCs)...

More Information


  1. Kuchen S, Resch W, Yamane A, Kuo N, Li Z, Chakraborty T, et al. Regulation of microRNA expression and abundance during lymphopoiesis. Immunity. 2010;32:828-39 pubmed publisher
    ..We applied miRNA-, mRNA-, and ChIP-Seq to characterize the microRNome during lymphopoiesis within the context of the transcriptome and epigenome...
  2. Zook E, Krishack P, Zhang S, Zeleznik Le N, Firulli A, Witte P, et al. Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells. Blood. 2011;118:5723-31 pubmed publisher
    ..Our data indicate that manipulation of Foxn1 expression in the thymus ameliorates thymopoiesis in aged mice and offer a strategy to combat the age-associated decline in naive T-cell production and CD4 naive/memory ratios in the elderly...
  3. Herzog S, Reth M, Jumaa H. Regulation of B-cell proliferation and differentiation by pre-B-cell receptor signalling. Nat Rev Immunol. 2009;9:195-205 pubmed publisher
    ..In this Review, we discuss how FOXO transcription factors are regulated by the pre-BCR to allow the progression of the cell cycle and the recombination of the light chain gene. ..
  4. Kee B. E and ID proteins branch out. Nat Rev Immunol. 2009;9:175-84 pubmed publisher
  5. Revilla i Domingo R, Bilic I, Vilagos B, Tagoh H, Ebert A, Tamir I, et al. The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis. EMBO J. 2012;31:3130-46 pubmed publisher
    ..Hence, Pax5 controls B-cell identity and function by regulating distinct target genes in early and late B lymphopoiesis.
  6. Jensen C, Kharazi S, Böiers C, Cheng M, Lübking A, Sitnicka E, et al. FLT3 ligand and not TSLP is the key regulator of IL-7-independent B-1 and B-2 B lymphopoiesis. Blood. 2008;112:2297-304 pubmed publisher
    ..Although IL-7 appears to be the primary cytokine regulator of fetal and adult B lymphopoiesis in mice, considerable fetal B lymphopoiesis and postnatal B cells are sustained in the absence of IL-7; in ..
  7. Schwickert T, Tagoh H, Gultekin S, Dakic A, Axelsson E, Minnich M, et al. Stage-specific control of early B cell development by the transcription factor Ikaros. Nat Immunol. 2014;15:283-93 pubmed publisher
    The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells...
  8. Chen X, Esplin B, Garrett K, Welner R, Webb C, Kincade P. Retinoids accelerate B lineage lymphoid differentiation. J Immunol. 2008;180:138-45 pubmed
    ..There may be previously unsuspected side effects of ATRA therapy, and the new findings suggest retinoids can normally contribute to the lymphopoietic environment in bone marrow. ..
  9. Wei G, Abraham B, Yagi R, Jothi R, Cui K, Sharma S, et al. Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types. Immunity. 2011;35:299-311 pubmed publisher
  10. Kreslavsky T, Gleimer M, von Boehmer H. Alphabeta versus gammadelta lineage choice at the first TCR-controlled checkpoint. Curr Opin Immunol. 2010;22:185-92 pubmed publisher
    ..Recent experiments support the former view. ..
  11. Okuyama K, Murata A, Sudo T, Yoshino M, Hayashi S. A checkpoint in B-lymphopoiesis related to Notch resistance. Biochem Biophys Res Commun. 2012;417:141-6 pubmed publisher
    While murine B- and T-lymphopoiesis require overlapping molecules, they occur in separate organs: the bone marrow (BM) and the thymus, respectively...
  12. Parra M. Epigenetic events during B lymphocyte development. Epigenetics. 2009;4:462-8 pubmed
    ..field have made significant advances towards understanding the contribution of transcription factors during B lymphopoiesis.They have established the existence of transcription factor networks that are essential for the proper ..
  13. Zhang Q, Iida R, Shimazu T, Kincade P. Replenishing B lymphocytes in health and disease. Curr Opin Immunol. 2012;24:196-203 pubmed publisher
    ..B lymphopoiesis is now seen as a gradual and unsynchronized process where progenitors eventually become B lineage restricted...
  14. Cochrane S, Zhao Y, Welner R, Sun X. Balance between Id and E proteins regulates myeloid-versus-lymphoid lineage decisions. Blood. 2009;113:1016-26 pubmed publisher
    ..Together, these results suggest a crucial function for E proteins in the myeloid-versus-lymphoid lineage decision. ..
  15. Malin S, McManus S, Cobaleda C, Novatchkova M, Delogu A, Bouillet P, et al. Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nat Immunol. 2010;11:171-9 pubmed publisher
    STAT5 and interleukin 7 (IL-7) signaling are thought to control B lymphopoiesis by regulating the expression of key transcription factors and by activating variable (V(H)) gene segments at the immunoglobulin heavy-chain (Igh) locus...
  16. Ichii M, Oritani K, Yokota T, Nishida M, Takahashi I, Shirogane T, et al. Regulation of human B lymphopoiesis by the transforming growth factor-beta superfamily in a newly established coculture system using human mesenchymal stem cells as a supportive microenvironment. Exp Hematol. 2008;36:587-97 pubmed publisher
    ..evaluated the negative-regulatory effects of the transforming growth factor (TGF)-beta superfamily on human B lymphopoiesis, and found that adding an anti-activin A antibody enhanced generation of CD10(+) cells two- to three-fold...
  17. Mansson R, Zandi S, Welinder E, Tsapogas P, Sakaguchi N, Bryder D, et al. Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity. Blood. 2010;115:2601-9 pubmed publisher
    ..These data suggest that the classic common lymphoid progenitor compartment composes a mixture of cells with relatively restricted lineage potentials, thus opening new possibilities to investigate early hematopoiesis...
  18. Gallo E, Ho L, Winslow M, Staton T, Crabtree G. Selective role of calcineurin in haematopoiesis and lymphopoiesis. EMBO Rep. 2008;9:1141-8 pubmed publisher
    ..The requirement for calcineurin/NFAT in the development of the adaptive but not of the innate immune system is consistent with the idea that the evolutionary appearance of this pathway was involved in the emergence of vertebrates. ..
  19. Vigliano I, Gorrese M, Fusco A, Vitiello L, Amorosi S, Panico L, et al. FOXN1 mutation abrogates prenatal T-cell development in humans. J Med Genet. 2011;48:413-6 pubmed publisher
    ..FOXN1 is crucial for in utero T cell development in humans. The identification of a limited number of CD8(+) cells suggests an extrathymic origin for these cells, implying FOXN1-independent lymphopoiesis.
  20. Li P, Burke S, Wang J, Chen X, Ortiz M, Lee S, et al. Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science. 2010;329:85-9 pubmed publisher
    ..Therefore, ITNKs may represent a new cell source for cell-based therapies. ..
  21. Kikuchi K, Kasai H, Watanabe A, Lai A, Kondo M. IL-7 specifies B cell fate at the common lymphoid progenitor to pre-proB transition stage by maintaining early B cell factor expression. J Immunol. 2008;181:383-92 pubmed
    ..However, it was not clear when IL-7 stimulation is necessary in hemato-/lymphopoiesis in adult mice...
  22. Peckl Schmid D, Wolkerstorfer S, Königsberger S, Achatz Straussberger G, Feichtner S, Schwaiger E, et al. HAX1 deficiency: impact on lymphopoiesis and B-cell development. Eur J Immunol. 2010;40:3161-72 pubmed publisher
    ..Hax1(-/-) B cells show a significantly reduced expression of CXCR4, which might have an influence on the observed defects in B-cell development. ..
  23. Zohren F, Souroullas G, Luo M, Gerdemann U, Imperato M, Wilson N, et al. The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors. Nat Immunol. 2012;13:761-9 pubmed publisher
    ..We identified Gfi1 as a critical transcriptional target of Lyl-1-mediated lymphopoiesis of T cells...
  24. Mega T, Lupia M, Amodio N, Horton S, Mesuraca M, Pelaggi D, et al. Zinc finger protein 521 antagonizes early B-cell factor 1 and modulates the B-lymphoid differentiation of primary hematopoietic progenitors. Cell Cycle. 2011;10:2129-39 pubmed
  25. Zhang Q, Iida R, Yokota T, Kincade P. Early events in lymphopoiesis: an update. Curr Opin Hematol. 2013;20:265-72 pubmed publisher
    ..While transcription factors have long been a focus of investigation, microRNAs are also being implicated in lymphopoiesis. Lymphocytes are normally replaced in correct proportion to other blood cells, but ratios change dramatically ..
  26. Sweeney E, Roberts D, Jacenko O. Altered matrix at the chondro-osseous junction leads to defects in lymphopoiesis. Ann N Y Acad Sci. 2011;1237:79-87 pubmed publisher
  27. Dudakov J, Goldberg G, Reiseger J, Chidgey A, Boyd R. Withdrawal of sex steroids reverses age- and chemotherapy-related defects in bone marrow lymphopoiesis. J Immunol. 2009;182:6247-60 pubmed publisher
    ..T cell production, there are also significant declines in B cell development and the progenitors that support lymphopoiesis. These collectively lead to a reduced peripheral immune repertoire, increase in opportunistic infections, and ..
  28. Zhang Z, Burnley P, Coder B, Su D. Insights on FoxN1 biological significance and usages of the "nude" mouse in studies of T-lymphopoiesis. Int J Biol Sci. 2012;8:1156-67 pubmed publisher
    ..We also raise questions and propose further consideration of FoxN1 functions and utilizing this mouse model for immune function studies. ..
  29. Lin Y, Jhunjhunwala S, Benner C, Heinz S, Welinder E, Mansson R, et al. A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. Nat Immunol. 2010;11:635-43 pubmed publisher
    ..From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate. ..
  30. Balkhi M, Willette Brown J, Zhu F, Chen Z, Liu S, Guttridge D, et al. IKK?-mediated signaling circuitry regulates early B lymphopoiesis during hematopoiesis. Blood. 2012;119:5467-77 pubmed publisher
    ..The results of the present study demonstrate that IKK? regulates B-lineage commitment via combined canonical and noncanonical NF-?B transcriptional activities to target Pax5 expression during hematopoiesis. ..
  31. Keren Z, Naor S, Nussbaum S, Golan K, Itkin T, Sasaki Y, et al. B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging. Blood. 2011;117:3104-12 pubmed publisher
    Aging is associated with a decline in B-lymphopoiesis in the bone marrow and accumulation of long-lived B cells in the periphery. These changes decrease the body's ability to mount protective antibody responses...
  32. Dias S, Mansson R, Gurbuxani S, Sigvardsson M, Kee B. E2A proteins promote development of lymphoid-primed multipotent progenitors. Immunity. 2008;29:217-27 pubmed publisher
    ..Our results reveal that E2A proteins play a critical role in supporting lymphoid specification from HSCs and that the reduced generation of LMPPs underlies the severe lymphocyte deficiencies observed in E2A-deficient mice. ..
  33. WU J, Purton L, Rodda S, Chen M, Weinstein L, McMahon A, et al. Osteoblastic regulation of B lymphopoiesis is mediated by Gs{alpha}-dependent signaling pathways. Proc Natl Acad Sci U S A. 2008;105:16976-81 pubmed publisher
    ..role in supporting hematopoietic development and recently have been implicated in the regulation of B lymphopoiesis. Here we demonstrate that the heterotrimeric G protein alpha subunit G(s)alpha is required in cells of the ..
  34. Corbeaux T, Hess I, Swann J, Kanzler B, Haas Assenbaum A, Boehm T. Thymopoiesis in mice depends on a Foxn1-positive thymic epithelial cell lineage. Proc Natl Acad Sci U S A. 2010;107:16613-8 pubmed publisher
    ..Our findings therefore support the notion that Foxn1 is the essential transcription factor regulating the differentiation of TECs and that its expression marks the major functional lineage of TECs in embryonic and adult thymic tissue...
  35. Greig K, de Graaf C, Murphy J, Carpinelli M, Pang S, Frampton J, et al. Critical roles for c-Myb in lymphoid priming and early B-cell development. Blood. 2010;115:2796-805 pubmed publisher
    ..c-Myb-deficient mice display reduced numbers of B cells; however, it is unknown what role c-Myb plays in B lymphopoiesis because no critical target genes have been identified in the B-cell lineage...
  36. Siewe B, Kalis S, Le P, Witte P, Choi S, Conway S, et al. In vitro requirement for periostin in B lymphopoiesis. Blood. 2011;117:3770-9 pubmed publisher
    B lymphopoiesis arrests in rabbits by 4 months of age...
  37. Welner R, Pelayo R, Kincade P. Evolving views on the genealogy of B cells. Nat Rev Immunol. 2008;8:95-106 pubmed publisher
    ..As we discuss in this Review, recent findings suggest that the process of B-cell formation is much more dynamic. ..
  38. Duchez S, Amin R, Cogne N, Delpy L, Sirac C, Pascal V, et al. Premature replacement of mu with alpha immunoglobulin chains impairs lymphopoiesis and mucosal homing but promotes plasma cell maturation. Proc Natl Acad Sci U S A. 2010;107:3064-9 pubmed publisher
    ..Our data indicate that the IgM BCR is more efficient in driving early B cell education and in mucosal site targeting, whereas the IgA BCR appears particularly suited to promoting activation and differentiation of effector plasma cells. ..
  39. Vomhof DeKrey E, Sandy A, Failing J, Hermann R, Hoselton S, Schuh J, et al. Radical reversal of vasoactive intestinal peptide (VIP) receptors during early lymphopoiesis. Peptides. 2011;32:2058-66 pubmed publisher
    ..that a high VPAC1:VPAC2 ratio in the earliest thymocyte progenitors (ETP cells) would be reversed during early lymphopoiesis as observed in activated, peripheral Th(2) cells, as the thymus is rich in Th(2) cytokines...
  40. Carpenter L, Malladi R, Yang C, French A, Pilkington K, Forsey R, et al. Human induced pluripotent stem cells are capable of B-cell lymphopoiesis. Blood. 2011;117:4008-11 pubmed publisher
    ..We therefore have been able to demonstrate, for the first time, that human iPS cells are able to undergo hematopoiesis that contributes to the B-cell lymphoid lineage. ..
  41. Sawa S, Cherrier M, Lochner M, Satoh Takayama N, Fehling H, Langa F, et al. Lineage relationship analysis of RORgammat+ innate lymphoid cells. Science. 2010;330:665-9 pubmed publisher
    ..Contrary to ROR?t(+) T cells, however, ROR?t(+) ILCs develop in the absence of microbiota. Our study indicates that ROR?t(+) ILCs evolve to preempt intestinal colonization by microbial symbionts...
  42. Yoshida T, Ng S, Georgopoulos K. Awakening lineage potential by Ikaros-mediated transcriptional priming. Curr Opin Immunol. 2010;22:154-60 pubmed publisher
    ..Loss of Ikaros removes the lymphoid leg of the immune system and may confer aberrant self-renewing properties to myeloid progenitors. ..
  43. Welner R, Esplin B, Garrett K, Pelayo R, Luche H, Fehling H, et al. Asynchronous RAG-1 expression during B lymphopoiesis. J Immunol. 2009;183:7768-77 pubmed publisher
    ..These findings indicate that essential events in B lymphopoiesis are not tightly synchronized...
  44. Song Z, Wang J, Guachalla L, Terszowski G, Rodewald H, Ju Z, et al. Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice. Blood. 2010;115:1481-9 pubmed publisher
    There is growing evidence that telomere dysfunction can contribute to human aging. Telomere dysfunction limits lymphopoiesis in aging telomerase knockout (mTerc(-/-)) mice primarily by the induction of stem cell-extrinsic alterations...
  45. Stehling Sun S, Dade J, Nutt S, DeKoter R, Camargo F. Regulation of lymphoid versus myeloid fate 'choice' by the transcription factor Mef2c. Nat Immunol. 2009;10:289-96 pubmed publisher
    ..1 during lymphopoiesis. Thus, Mef2c is a crucial component of the transcriptional network that regulates cell fate 'choice' in ..
  46. Lukin K, Fields S, Guerrettaz L, Straign D, Rodriguez V, Zandi S, et al. A dose-dependent role for EBF1 in repressing non-B-cell-specific genes. Eur J Immunol. 2011;41:1787-93 pubmed publisher
    ..Previously, we investigated the roles of EBF1 and its DNA-binding partner Runx1 by evaluating B lymphopoiesis in single (EBF1(het) and Runx1(het)) and compound haploinsufficent (Ebf1(+/-) Runx1(+/-), ER(het)) mice...
  47. Yokota T, Oritani K, Garrett K, Kouro T, Nishida M, Takahashi I, et al. Soluble frizzled-related protein 1 is estrogen inducible in bone marrow stromal cells and suppresses the earliest events in lymphopoiesis. J Immunol. 2008;181:6061-72 pubmed
    It has long been known that lymphopoiesis is transiently suppressed during pregnancy, which can be experimentally simulated by estrogen treatment...
  48. Huin Schohn C, Guéguinou N, Schenten V, Bascove M, Koch G, Baatout S, et al. Gravity changes during animal development affect IgM heavy-chain transcription and probably lymphopoiesis. FASEB J. 2013;27:333-41 pubmed publisher
    ..Taken together, and given that the larvae were not immunized, these data suggest a modification of lymphopoiesis when gravity changes occur during ontogeny.
  49. Milne C, Corfe S, Paige C. Heparan sulfate and heparin enhance ERK phosphorylation and mediate preBCR-dependent events during B lymphopoiesis. J Immunol. 2008;180:2839-47 pubmed
    ..Heparan sulfates are present on stromal cells and B lineage cells present in hemopoietic tissues and may provide stimulation to preB cells testing the signaling capacity of the preBCR. ..
  50. Decker T, Pasca di Magliano M, McManus S, Sun Q, Bonifer C, Tagoh H, et al. Stepwise activation of enhancer and promoter regions of the B cell commitment gene Pax5 in early lymphopoiesis. Immunity. 2009;30:508-20 pubmed publisher
    ..These experiments demonstrate a stepwise activation of Pax5 in early lymphopoiesis and provide mechanistic insights into the process of B cell commitment.
  51. Lu Y, Zhang H. [Effects of electroacupuncture on T-lymphocytes, spleen index, thymus index and lymphopoiesis levels in strenuous exercise-induced stress rats]. Zhen Ci Yan Jiu. 2012;37:136-9 pubmed
    To observe the effect of electroacupuncture (EA) on levels of T-lymphocytes, spleen index, thymus index and lymphopoiesis in strenuous exercise-induced immunosuppression rats, so as to study its mechanisms underlying improving immune ..
  52. Bilwani F, Knight K. Adipocyte-derived soluble factor(s) inhibits early stages of B lymphopoiesis. J Immunol. 2012;189:4379-86 pubmed publisher
    B lymphopoiesis declines with age, and in rabbits this occurs by 8 wk of age...
  53. Staal F, Sen J. The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis. Eur J Immunol. 2008;38:1788-94 pubmed publisher
    ..that a large body of gain-of-function and loss-of-function studies implicate Wnt-beta-catenin signaling in lymphopoiesis and hematopoiesis...