Two Pathways of B‐Lymphocyte Development in Mouse Bone Marrow and the Roles of Surrogate L Chain in this Development

The commitment of pluripotent stem cells and lymphoid progenitors to the Blineage pathway of differentiation in bone marrow of mice has been investigated in many laboratories. One aim of such studies is to analyze the molecular steps and cellular stages in which B-lineage progenitors and precursors rearrange immunoglobulin (Ig) heavy (H) and light (L) chain gene segments (V, D, J) to express first H, then L chains, and thereby generate a potential repertoire of B lymphocytes. The selection of these cells into a repertoire available in the peripheral pool of mature B cells has also been extensively examined (for reviews see Osmond 1991, Tsubata & Nishikawa 1991, Hardy 1992, Rajewsky 1992, Chen & Alt 1993, Rolink & Melchers 1993a, b). Fig. 1 summarizes some of our current knowledge of the size and cell cycle status of the major B-lineage precursor subpopulations in bone marrow, their expression of markers, and their potential for in vitro proliferation and for in vivo transplantability. It describes two pathways of differentiation, one of which (pathway 1) selects for productively H chain-gene-rearranged, fiH chain-expressing precursors, while the other pathway (2) appears to occur without selection for products of Ig gene rearrangements, and will proceed via a cellular program of surface marker and functional changes even without Ig-gene rearrangements. These two pathways will be explained in more detail. In this review article we summarize our recent work which is concerned with

[1]  A. Rolink,et al.  Rearrangement and expression of χ light chain genes can occur without μ heavy chain expression during differentiation of pre-B cells , 1993 .

[2]  A. Strasser,et al.  Immature surface Ig+ B cells can continue to rearrange kappa and lambda L chain gene loci , 1993, The Journal of experimental medicine.

[3]  H. Karasuyama,et al.  A complex of glycoproteins is associated with VpreB/lambda 5 surrogate light chain on the surface of mu heavy chain-negative early precursor B cell lines , 1993, The Journal of experimental medicine.

[4]  M. Lieber,et al.  Extent to which homology can constrain coding exon junctional diversity in V(D)J recombination , 1993, Nature.

[5]  K. Rajewsky,et al.  Deletion of the immunoglobulin kappa chain intron enhancer abolishes kappa chain gene rearrangement in cis but not lambda chain gene rearrangement in trans. , 1993, The EMBO journal.

[6]  A. Rolink,et al.  B cell development in mice with a defective λ5 gene , 1993, European journal of immunology.

[7]  F. Melchers,et al.  Changes in frequencies of clonable pre B cells during life in different lymphoid organs of mice. , 1993, Blood.

[8]  K. Rajewsky,et al.  Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development , 1993, Cell.

[9]  F. Alt,et al.  B cell development in mice that lack one or both immunoglobulin kappa light chain genes. , 1993, The EMBO journal.

[10]  K. Rajewsky,et al.  Gene targeting in the Ig kappa locus: efficient generation of lambda chain‐expressing B cells, independent of gene rearrangements in Ig kappa. , 1993, The EMBO journal.

[11]  J. Kearney,et al.  The expression of the mouse VpreB/lambda 5 locus in transformed cell lines and tumors of the B lineage differentiation pathway. , 1992, International immunology.

[12]  F. Alt,et al.  Surface IgM mediated regulation of RAG gene expression in E mu‐N‐myc B cell lines. , 1992, The EMBO journal.

[13]  K. Rajewsky.  Early and late B-cell development in the mouse , 1992, Current Biology.

[14]  K. Rajewsky,et al.  A critical role of λ5 protein in B cell development , 1992, Cell.

[15]  Gillian E. Wu,et al.  Enumeration and characterization of DJH structures in mouse fetal liver. , 1992, The EMBO journal.

[16]  V. Stewart,et al.  RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement , 1992, Cell.

[17]  Susumu Tonegawa,et al.  RAG-1-deficient mice have no mature B and T lymphocytes , 1992, Cell.

[18]  D. Ramsden,et al.  Mouse kappa light-chain recombination signal sequences mediate recombination more frequently than do those of lambda light chain. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[19]  H. Yamagishi,et al.  Deletions of immunoglobulin C kappa region characterized by the circular excision products in mouse splenocytes , 1991, The Journal of experimental medicine.

[20]  K. Rajewsky,et al.  B cell development regulated by gene rearrangement: Arrest of maturation by membrane-bound Dμ protein and selection of DH element reading frames , 1991, Cell.

[21]  Klaus Rajewsky,et al.  A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin μ chain gene , 1991, Nature.

[22]  H. Yamagishi,et al.  Lack of feedback inhibition of V kappa gene rearrangement by productively rearranged alleles , 1991, The Journal of experimental medicine.

[23]  J. Koziol,et al.  The expression of the Ig H chain repertoire in developing bone marrow B lineage cells. , 1991, Journal of immunology.

[24]  A. Feeney.  Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences , 1990, The Journal of experimental medicine.

[25]  K. Rajewsky,et al.  Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B‐CLL progenitor generation. , 1990, The EMBO journal.

[26]  K. Rajewsky,et al.  The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Jean-Claude Weill,et al.  Somatic hyperconversion diversifies the single VH gene of the chicken with a high incidence in the D region , 1989, Cell.

[28]  D. Baltimore,et al.  Activation of immunoglobulin kappa gene rearrangement correlates with induction of germline kappa gene transcription , 1989, Cell.

[29]  S. Levy,et al.  Functional immunoglobulin light chain genes are replaced by ongoing rearrangements of germline V kappa genes to downstream J kappa segment in a murine B cell line , 1989, The Journal of experimental medicine.

[30]  A. Carroll,et al.  Light-chain gene expression before heavy-chain gene rearrangement in pre-B cells transformed by Epstein-Barr virus. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[31]  F. Melchers,et al.  A second gene, VpreB in the lambda 5 locus of the mouse, which appears to be selectively expressed in pre‐B lymphocytes. , 1987, The EMBO journal.

[32]  E. Selsing,et al.  Active lambda and kappa antibody gene rearrangement in Abelson murine leukemia virus-transformed pre-B cell lines , 1987, The Journal of experimental medicine.

[33]  F. Melchers,et al.  λ5, a new light-chain-related locus selectively expressed in pre-B lymphocytes , 1986, Nature.

[34]  J. Dangl,et al.  Frequent lambda light chain gene rearrangement and expression in a Ly-1 B lymphoma with a productive kappa chain allele. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[35]  O. Mäkelä,et al.  Reading of D genes in variable frames as a source of antibody diversity. , 1985, Immunology today.

[36]  F. Alt,et al.  Developmentally controlled and tissue-specific expression of unrearranged VH gene segments , 1985, Cell.

[37]  R. Custer,et al.  A severe combined immunodeficiency mutation in the mouse , 1983, Nature.

[38]  S. Aaronson,et al.  BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell , 1982, The Journal of experimental medicine.

[39]  B. Ness,et al.  Transcription of the unrearranged mouse Cκ locus: Sequence of the initiation region and comparison of activity with a rearranged Vκ-Cκ gene , 1981, Cell.

[40]  R. Perry,et al.  Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression , 1981, Nature.

[41]  Y. Bergman,et al.  An IgM‐producing tumor with biochemical characteristics of a small B lymphocyte , 1977, European journal of immunology.

[42]  T. Winkler,et al.  Roles of IgH and L chains and of surrogate H and L chains in the development of cells of the B lymphocyte lineage. , 1994, Annual review of immunology.

[43]  F. Melchers,et al.  Influence of surrogate L chain on DHJH-reading frame 2 suppression in mouse precursor B cells. , 1994, International immunology.

[44]  S. Bauer,et al.  The surrogate light chain in B-cell development. , 1993, Immunology today.

[45]  A. Rolink,et al.  Generation and regeneration of cells of the B-lymphocyte lineage. , 1993, Current opinion in immunology.

[46]  A. Rolink,et al.  B lymphopoiesis in the mouse. , 1993, Advances in immunology.

[47]  F. Alt,et al.  Gene rearrangement and B-cell development. , 1993, Current opinion in immunology.

[48]  R. Hardy.  Variable gene usage, physiology and development of Ly-1+ (CD5+) B cells. , 1992, Current opinion in immunology.

[49]  D. G. Osmond,et al.  Proliferation kinetics and the lifespan of B cells in central and peripheral lymphoid organs. , 1991, Current opinion in immunology.

[50]  S. Nishikawa,et al.  Molecular and cellular aspects of early B-cell development. , 1991, Current opinion in immunology.

[51]  S. Bauer,et al.  Structure, Control of Expression and Putative Function of the PreB Cell-Specific Genes VpreB and λ5 , 1989 .

[52]  M. Campbell,et al.  Functional Immunoglobulin Light Chain Genes Are Replaced by Ongoing Rearrangements of Germline Vk Genes to Downstream Jk Segments in a Murine B Cell Line , 1989 .

[53]  阪口 薫雄.  λ5, a new light-chain-related locus selectively expressed in pre-B lymphocytes , 1987 .

[54]  M. Reth,et al.  A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production , 1986, Nature.

[55]  F. Alt,et al.  Regulated progression of a cultured pre-B-cell line to the B-cell stage , 1985, Nature.

[56]  Gillian E. Wu,et al.  Mouse K light-chain recombination signal sequences mediate recombination more frequently than do those of A light chain ( immunoglobulin gene rearrangement / isotype exclusion ) , 2022 .