Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 19 April 1996:
Vol. 272. no. 5260, pp. 411 - 414
DOI: 10.1126/science.272.5260.411
Prev | Table of Contents | Next

Reports

Regulation of an Early Developmental Checkpoint in the B Cell Pathway by Igbeta

Shiaoching Gong and Michel C. Nussenzweig *

Many of the cell fate decisions in precursor B cells and more mature B cells are controlled by membrane immunoglobulin (Ig) M heavy chain (mµ) and the Igalpha -Igbeta signal transducers. The role of Igbeta in regulating early B cell development was examined in mice that lack Igbeta (Igbeta -/-). These mice had a complete block in B cell development at the immature CD43+B220+ stage. Immunoglobulin heavy chain diversity (DH) and joining (JH) segments rearranged, but variable (VH) to DJH recombination and immunoglobulin messenger RNA expression were compromised. These experiments define an unexpected, early requirement for Igbeta to produce B cells that can complete VDJH recombination.

Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA.
* To whom correspondence should be addressed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Combinatorial surrobody libraries.
L. Xu, H. Yee, C. Chan, A. K. Kashyap, L. Horowitz, M. Horowitz, R. R. Bhatt, and R. A. Lerner (2008)
PNAS 105, 10756-10761
   Abstract »    Full Text »    PDF »
Maintenance of Surrogate Light Chain Expression Induces Developmental Delay in Early B Cell Compartment.
D. A. Martin, L. Lu, M. Cascalho, and G. E. Wu (2007)
J. Immunol. 179, 4996-5005
   Abstract »    Full Text »    PDF »
Mutations of the Ig{beta} gene cause agammaglobulinemia in man.
S. Ferrari, V. Lougaris, S. Caraffi, R. Zuntini, J. Yang, A. Soresina, A. Meini, G. Cazzola, C. Rossi, M. Reth, et al. (2007)
J. Exp. Med. 204, 2047-2051
   Abstract »    Full Text »    PDF »
Cutting Edge: A Hypomorphic Mutation in Igbeta (CD79b) in a Patient with Immunodeficiency and a Leaky Defect in B Cell Development.
A. K. Dobbs, T. Yang, D. Farmer, L. Kager, O. Parolini, and M. E. Conley (2007)
J. Immunol. 179, 2055-2059
   Abstract »    Full Text »    PDF »
IFN Regulatory Factor 4 and 8 Promote Ig Light Chain {kappa} Locus Activation in Pre-B Cell Development.
S. Ma, A. Turetsky, L. Trinh, and R. Lu (2006)
J. Immunol. 177, 7898-7904
   Abstract »    Full Text »    PDF »
Lower levels of surface B-cell-receptor expression in chronic lymphocytic leukemia are associated with glycosylation and folding defects of the {micro} and CD79a chains.
F. Vuillier, G. Dumas, C. Magnac, M.-C. Prevost, A. I. Lalanne, P. Oppezzo, E. Melanitou, G. Dighiero, and B. Payelle-Brogard (2005)
Blood 105, 2933-2940
   Abstract »    Full Text »    PDF »
Basal Ig{alpha}/Ig{beta} Signals Trigger the Coordinated Initiation of Pre-B Cell Antigen Receptor-Dependent Processes.
E. M. Fuentes-Panana, G. Bannish, N. Shah, and J. G. Monroe (2004)
J. Immunol. 173, 1000-1011
   Abstract »    Full Text »    PDF »
Pax5 Activates Immunoglobulin Heavy Chain V to DJ Rearrangement in Transgenic Thymocytes.
L.-Y. Hsu, H.-E. Liang, K. Johnson, C. Kang, and M. S. Schlissel (2004)
J. Exp. Med. 199, 825-830
   Abstract »    Full Text »    PDF »
The Cytoplasmic Domain of Ig{alpha} Is Necessary and Sufficient to Support Efficient Early B Cell Development.
K. A. Pike, S. Iacampo, J. E. Friedmann, and M. J. H. Ratcliffe (2004)
J. Immunol. 172, 2210-2218
   Abstract »    Full Text »    PDF »
Selection of B lymphocytes in the periphery is determined by the functional capacity of the B cell antigen receptor.
L. D. Wang, J. Lopes, A. B. Cooper, M. Dang-Lawson, L. Matsuuchi, and M. R. Clark (2004)
PNAS 101, 1027-1032
   Abstract »    Full Text »    PDF »
Identification of a Pre-BCR Lacking Surrogate Light Chain.
Y.-w. Su, A. Flemming, T. Wossning, E. Hobeika, M. Reth, and H. Jumaa (2003)
J. Exp. Med. 198, 1699-1706
   Abstract »    Full Text »    PDF »
CD19 Function in Early and Late B Cell Development. II. CD19 Facilitates the Pro-B/Pre-B Transition.
D. C. Otero and R. C. Rickert (2003)
J. Immunol. 171, 5921-5930
   Abstract »    Full Text »    PDF »
Cutting Edge: Signaling and Cell Surface Expression of a {micro}H Chain in the Absence of {lambda}5: A Paradigm Revisited.
W. Schuh, S. Meister, E. Roth, and H.-M. Jack (2003)
J. Immunol. 171, 3343-3347
   Abstract »    Full Text »    PDF »
Immunoglobulin {micro} Heavy Chains Do Not Mediate Tyrosine Phosphorylation of Ig{alpha} from the ER-cis-Golgi.
D. Mielenz, A. Ruschel, C. Vettermann, and H.-M. Jack (2003)
J. Immunol. 171, 3091-3101
   Abstract »    Full Text »    PDF »
IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development.
R. Lu, K. L. Medina, D. W. Lancki, and H. Singh (2003)
Genes & Dev. 17, 1703-1708
   Abstract »    Full Text »    PDF »
Lack of the Transcriptional Coactivator OBF-1 Prevents the Development of Systemic Lupus Erythematosus-Like Phenotypes in Aiolos Mutant Mice.
J. Sun, G. Matthias, M. J. Mihatsch, K. Georgopoulos, and P. Matthias (2003)
J. Immunol. 170, 1699-1706
   Abstract »    Full Text »    PDF »
Block in Development at the Pre-B-II to Immature B Cell Stage in Mice Without Ig{kappa} and Ig{lambda} Light Chain.
X. Zou, T. A. Piper, J. A. Smith, N. D. Allen, J. Xian, and M. Bruggemann (2003)
J. Immunol. 170, 1354-1361
   Abstract »    Full Text »    PDF »
Disseminated Candidiasis and Hepatic Malarial Infection in Mannose-Binding-Lectin-A-Deficient Mice.
S. J. Lee, G. Gonzalez-Aseguinolaza, and M. C. Nussenzweig (2002)
Mol. Cell. Biol. 22, 8199-8203
   Abstract »    Full Text »    PDF »
Cooperative interaction of Ig{alpha} and Ig{beta} of the BCR regulates the kinetics and specificity of antigen targeting.
C. Li, K. Siemasko, M. R. Clark, and W. Song (2002)
Int. Immunol. 14, 1179-1191
   Abstract »    Full Text »    PDF »
Expression of Human Complement Receptor Type 2 (CD21) in Mice During Early B Cell Development Results in a Reduction in Mature B Cells and Hypogammaglobulinemia.
K. J. Marchbank, L. Kulik, M. G. Gipson, B. P. Morgan, and V. M. Holers (2002)
J. Immunol. 169, 3526-3535
   Abstract »    Full Text »    PDF »
Deletion of immunoglobulin beta in developing B cells leads to cell death.
E. Meffre and M. C. Nussenzweig (2002)
PNAS 99, 11334-11339
   Abstract »    Full Text »    PDF »
Delayed Cellular Maturation and Decreased Immunoglobulin {kappa} Light Chain Production In Immature B Lymphocytes Lacking B Cell Linker Protein.
S. Xu and K.-P. Lam (2002)
J. Exp. Med. 196, 197-206
   Abstract »    Full Text »    PDF »
B Cell Progenitors Are Arrested in Maturation but Have Intact VDJ Recombination in the Absence of Ig-{alpha} and Ig-{beta}.
R. Pelanda, U. Braun, E. Hobeika, M. C. Nussenzweig, and M. Reth (2002)
J. Immunol. 169, 865-872
   Abstract »    Full Text »    PDF »
The Human V-PreB Promoter Is a Target for Coordinated Activation by Early B Cell Factor and E47.
R. Gisler and M. Sigvardsson (2002)
J. Immunol. 168, 5130-5138
   Abstract »    Full Text »    PDF »
Bob1 (OCA-B/OBF-1) Differential Transactivation of the B Cell-Specific B29 (Ig{beta}) and mb-1 (Ig{alpha}) Promoters.
C. S. Malone and R. Wall (2002)
J. Immunol. 168, 3369-3375
   Abstract »    Full Text »    PDF »
Differential surrogate light chain expression governs B-cell differentiation.
Y.-H. Wang, R. P. Stephan, A. Scheffold, D. Kunkel, H. Karasuyama, A. Radbruch, and M. D. Cooper (2002)
Blood 99, 2459-2467
   Abstract »    Full Text »    PDF »
Impaired Precursor B Cell Differentiation in Bruton's Tyrosine Kinase-Deficient Mice.
S. Middendorp, G. M. Dingjan, and R. W. Hendriks (2002)
J. Immunol. 168, 2695-2703
   Abstract »    Full Text »    PDF »
Characterization of T Cell Differentiation in the Murine Gut.
F. Lambolez, O. Azogui, A.-M. Joret, C. Garcia, H. von Boehmer, J. Di Santo, S. Ezine, and B. Rocha (2002)
J. Exp. Med. 195, 437-449
   Abstract »    Full Text »    PDF »
TDAG51 Is Not Essential for Fas/CD95 Regulation and Apoptosis In Vivo.
J. Rho, S. Gong, N. Kim, and Y. Choi (2001)
Mol. Cell. Biol. 21, 8365-8370
   Abstract »    Full Text »    PDF »
xid mice reveal the interplay of homeostasis and Bruton's tyrosine kinase-mediated selection at multiple stages of B cell development.
M. P. Cancro, A. P. Sah, S. L. Levy, D. M. Allman, M. R. Schmidt, and R. T. Woodland (2001)
Int. Immunol. 13, 1501-1514
   Abstract »    Full Text »    PDF »
Ligand-independent Signaling Functions for the B Lymphocyte Antigen Receptor and Their Role in Positive Selection during B Lymphopoiesis.
G. Bannish, E. M. Fuentes-Panana, J. C. Cambier, W. S. Pear, and J. G. Monroe (2001)
J. Exp. Med. 194, 1583-1596
   Abstract »    Full Text »    PDF »
Analysis of VpreB Expression During B Lineage Differentiation in {lambda}5-Deficient Mice.
R. P. Stephan, E. Elgavish, H. Karasuyama, H. Kubagawa, and M. D. Cooper (2001)
J. Immunol. 167, 3734-3739
   Abstract »    Full Text »    PDF »
Interference with Immunoglobulin (Ig){alpha} Immunoreceptor Tyrosine-Based Activation Motif (Itam) Phosphorylation Modulates or Blocks B Cell Development, Depending on the Availability of an Ig{beta} Cytoplasmic Tail.
M. Kraus, L. I. Pao, A. Reichlin, Y. Hu, B. Canono, J. C. Cambier, M. C. Nussenzweig, and K. Rajewsky (2001)
J. Exp. Med. 194, 455-470
   Abstract »    Full Text »    PDF »
A VH12 Transgenic Mouse Exhibits Defects in Pre-B Cell Development and Is Unable to Make IgM+ B Cells.
H. Wang, J. Ye, L. W. Arnold, S. K. McCray, and S. H. Clarke (2001)
J. Immunol. 167, 1254-1262
   Abstract »    Full Text »    PDF »
Involvement of Bik, a Proapoptotic Member of the Bcl-2 Family, in Surface IgM-Mediated B Cell Apoptosis.
A. Jiang and E. A. Clark (2001)
J. Immunol. 166, 6025-6033
   Abstract »    Full Text »    PDF »
Bruton's tyrosine kinase is required for signaling the CD79b-mediated pro-B to pre-B cell transition.
T. Kouro, K. Nagata, S. Takaki, S. Nisitani, M. Hirano, M. I. Wahl, O. N. Witte, H. Karasuyama, and K. Takatsu (2001)
Int. Immunol. 13, 485-493
   Abstract »    Full Text »    PDF »
B Cell Development Is Arrested at the Immature B Cell Stage in Mice Carrying a Mutation in the Cytoplasmic Domain of Immunoglobulin {beta}.
A. Reichlin, Y. Hu, E. Meffre, H. Nagaoka, S. Gong, M. Kraus, K. Rajewsky, and M. C. Nussenzweig (2001)
J. Exp. Med. 193, 13-24
   Abstract »    Full Text »    PDF »
Cutting Edge: B Cell Linker Protein Is Dispensable for the Allelic Exclusion of Immunoglobulin Heavy Chain Locus But Required for the Persistence of CD5+ B Cells.
S. Xu, S.-C. Wong, and K.-P. Lam (2000)
J. Immunol. 165, 4153-4157
   Abstract »    Full Text »    PDF »
The level of expression of {micro} heavy chain modifies the composition of peripheral B cell subpopulations.
P. Sanchez, A.-M. Crain-Denoyelle, P. Daras, M.-C. Gendron, and C. Kanellopoulos-Langevin (2000)
Int. Immunol. 12, 1459-1466
   Abstract »    Full Text »    PDF »
Aberrant Trafficking of the B Cell Receptor Ig-{alpha}{beta} Subunit in a B Lymphoma Cell Line.
C. Condon, S. L. Hourihane, M. Dang-Lawson, J. Escribano, and L. Matsuuchi (2000)
J. Immunol. 165, 1427-1437
   Abstract »    Full Text »    PDF »
Fates of human B-cell precursors.
T. W. LeBien (2000)
Blood 96, 9-23
   Abstract »    Full Text »    PDF »
Differential Regulation of B Cell Development, Activation, and Death by the Src Homology 2 Domain-Containing 5' Inositol Phosphatase (Ship).
A. Brauweiler, I. Tamir, J. Dal Porto, R. J. Benschop, C. D. Helgason, R. K. Humphries, J. H. Freed, and J. C. Cambier (2000)
J. Exp. Med. 191, 1545-1554
   Abstract »    Full Text »    PDF »
An Upstream Oct-1- and Oct-2-Binding Silencer Governs B29 (Ig{beta}) Gene Expression.
C. S. Malone, L. Patrone, K. L. Buchanan, C. F. Webb, and R. Wall (2000)
J. Immunol. 164, 2550-2556
   Abstract »    Full Text »    PDF »
Epstein-Barr Virus LMP2A-Induced B-Cell Survival in Two Unique Classes of E{micro}LMP2A Transgenic Mice.
R. G. Caldwell, R. C. Brown, and R. Longnecker (2000)
J. Virol. 74, 1101-1113
   Abstract »    Full Text »    PDF »
Differential effect of an Ig {micro} transgene on development of pre-B cells in fetal and adult SCID mice.
G. C. Bosma, Y. Chang, H. Karasuyama, and M. J. Bosma (1999)
PNAS 96, 11952-11957
   Abstract »    Full Text »    PDF »
The CH1 and transmembrane domains of {micro} in the context of a {gamma}2b transgene do not suffice to promote B cell maturation.
X. Shen, G. Bozek, C. A. Pinkert, and U. Storb (1999)
Int. Immunol. 11, 1663-1671
   Abstract »    Full Text »    PDF »
Pro-B-Cell-Specific Transcription and Proapoptotic Function of Protein Kinase Ceta.
T. A. Morrow, S. A. Muljo, J. Zhang, J. M. Hardwick, and M. S. Schlissel (1999)
Mol. Cell. Biol. 19, 5608-5618
   Abstract »    Full Text »    PDF »
Modifications of Igalpha and Igbeta Expression as a Function of B Lineage Differentiation.
K. Benlagha, P. Guglielmi, M. D. Cooper, and K. Lassoued (1999)
J. Biol. Chem. 274, 19389-19396
   Abstract »    Full Text »    PDF »
Ig{alpha} and Ig{beta} Are Required for Efficient Trafficking to Late Endosomes and to Enhance Antigen Presentation.
K. Siemasko, B. J. Eisfelder, C. Stebbins, S. Kabak, A. J. Sant, W. Song, and M. R. Clark (1999)
J. Immunol. 162, 6518-6525
   Abstract »    Full Text »    PDF »
Extended Duration of DH-JH Rearrangement in Immunoglobulin Heavy Chain Transgenic Mice: Implications for Regulation of Allelic Exclusion.
Y. Chang, M. J. Bosma, and G. C. Bosma (1999)
J. Exp. Med. 189, 1295-1305
   Abstract »    Full Text »    PDF »
Type I IFN sets the stringency of B cell repertoire selection in the bone marrow.
R. Vasconcellos, D. Braun, A. Coutinho, and J. Demengeot (1999)
Int. Immunol. 11, 279-288
   Abstract »    Full Text »    PDF »
Activated Ras Signals Developmental Progression of Recombinase-activating Gene (RAG)-deficient Pro-B Lymphocytes.
A. C. Shaw, W. Swat, R. Ferrini, L. Davidson, and F. W. Alt (1999)
J. Exp. Med. 189, 123-129
   Abstract »    Full Text »    PDF »
The B29 (Immunoglobulin beta -Chain) Gene Is a Genetic Target for Early B-Cell Factor.
P. Akerblad, M. Rosberg, T. Leanderson, and M. Sigvardsson (1999)
Mol. Cell. Biol. 19, 392-401
   Abstract »    Full Text »    PDF »
Requirement of CD3 Complex-associated Signaling Functions for Expression of Rearranged T Cell Receptor {beta} VDJ Genes in Early Thymic Development.
A. Wurch, J. Biro, A. J. Potocnik, I. Falk, H. Mossmann, and K. Eichmann (1998)
J. Exp. Med. 188, 1669-1678
   Abstract »    Full Text »    PDF »
Independent and Opposing Roles For Btk and Lyn in B and Myeloid Signaling Pathways.
A. B. Satterthwaite, C. A. Lowell, W. N. Khan, P. Sideras, F. W. Alt, and O. N. Witte (1998)
J. Exp. Med. 188, 833-844
   Abstract »    Full Text »    PDF »
Early Function of Pax5 (BSAP) before the Pre-B Cell Receptor Stage of B Lymphopoiesis.
C. Thevenin, S. L. Nutt, and M. Busslinger (1998)
J. Exp. Med. 188, 735-744
   Abstract »    Full Text »    PDF »
Intestinal intraepithelial lymphocytes include precursors committed to the T cell receptor alpha beta lineage.
S. T. Page, L. Y. Bogatzki, J. A. Hamerman, C. H. Sweenie, P. J. Hogarth, M. Malissen, R. M. Perlmutter, and A. M. Pullen (1998)
PNAS 95, 9459-9464
   Abstract »    Full Text »    PDF »
Surrogate Light Chain Production During B Cell Differentiation: Differential Intracellular Versus Cell Surface Expression.
Y.-H. Wang, J. Nomura, O. M. Faye-Petersen, and M. D. Cooper (1998)
J. Immunol. 161, 1132-1139
   Abstract »    Full Text »    PDF »
Role of {micro} Heavy Chain in B Cell Development. I. Blocked B Cell Maturation But Complete Allelic Exclusion in the Absence of Ig{alpha}/{beta}.
F. E. Cronin, M. Jiang, A. K. Abbas, and S. A. Grupp (1998)
J. Immunol. 161, 252-259
   Abstract »    Full Text »    PDF »
Cross-lineage expression of Ig-beta (B29) in thymocytes: Positive and negative gene regulation to establish T cell identity.
H. Wang, R. A. Diamond, and E. V. Rothenberg (1998)
PNAS 95, 6831-6836
   Abstract »    Full Text »    PDF »
Natural and Engineered Disorders of Lymphocyte Development.
A. Fischer and B. Malissen (1998)
Science 280, 237-243
   Abstract »    Full Text »
Biochemical and Functional Analyses of Chromatin Changes at the TCR-{beta} Gene Locus During CD4-CD8- to CD4+CD8+ Thymocyte Differentiation.
S. Chattopadhyay, C. E. Whitehurst, F. Schwenk, and J. Chen (1998)
J. Immunol. 160, 1256-1267
   Abstract »    Full Text »    PDF »
The CD3-{gamma}{delta}{varepsilon} and CD3-{zeta}/{eta} Modules Are Each Essential for Allelic Exclusion at the T Cell Receptor {beta} Locus but Are Both Dispensable for the Initiation of V to (D)J Recombination at the T Cell Receptor-{beta}, -{gamma}, and -{delta} Loci.
L. Ardouin, J. Ismaili, B. Malissen, and M. Malissen (1998)
J. Exp. Med. 187, 105-116
   Abstract »    Full Text »    PDF »
Silencer elements controlling the B29 (Igbeta ) promoter are neither promoter- nor cell-type-specific.
C. S. Malone, S. A. Omori, and R. Wall (1997)
PNAS 94, 12314-12319
   Abstract »    Full Text »    PDF »
Aberrations of the B-Cell Receptor B29 (CD79b) Gene in Chronic Lymphocytic Leukemia.
A. A. Thompson, J. A. Talley, H. N. Do, H. L. Kagan, L. Kunkel, J. Berenson, M. D. Cooper, A. Saxon, and R. Wall (1997)
Blood 90, 1387-1394
   Abstract »    Full Text »    PDF »
The Immunoglobulin (Ig){alpha} and Ig{beta} Cytoplasmic Domains Are Independently Sufficient to Signal B Cell Maturation and Activation in Transgenic Mice.
Y.-M. Teh and M. S. Neuberger (1997)
J. Exp. Med. 185, 1753-1758
   Abstract »    Full Text »    PDF »
Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus..
S L Nutt, P Urbanek, A Rolink, and M Busslinger (1997)
Genes & Dev. 11, 476-491
   Abstract »    PDF »
Counterselection against D{micro} Is Mediated through Immunoglobulin (Ig){alpha}-Ig{beta}.
S. Gong, M. Sanchez, and M. C. Nussenzweig (1996)
J. Exp. Med. 184, 2079-2084
   Abstract »    Full Text »    PDF »
AKT Induces Transcriptional Activity of PU.1 through Phosphorylation-mediated Modifications within Its Transactivation Domain.
P. Rieske and J. M. R. Pongubala (2001)
J. Biol. Chem. 276, 8460-8468
   Abstract »    Full Text »    PDF »
Induction of pre-B cell proliferation after de novo synthesis of the pre-B cell receptor.
J. Hess, A. Werner, T. Wirth, F. Melchers, H.-M. Jack, and T. H. Winkler (2001)
PNAS 98, 1745-1750
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)