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 14 June 1996:
Vol. 272. no. 5268, pp. 1649 - 1652
DOI: 10.1126/science.272.5268.1649
Prev | Table of Contents | Next

Reports

A Quasi-Monoclonal Mouse

Marilia Cascalho, Audrey Ma, Steven Lee, Linda Masat, Matthias Wabl

As a model for studying the generation of antibody diversity, a gene-targeted mouse was produced that is hemizygous for a rearranged V(D)J segment at the immunoglobulin (Ig) heavy chain locus, the other allele being nonfunctional. The mouse also has no functional kappa light chain allele. The heavy chain, when paired with any lambda light chain, is specific for the hapten (4-hydroxy-3-nitrophenyl) acetyl (NP). The primary repertoire of this quasi-monoclonal mouse is monospecific, but somatic hypermutation and secondary rearrangements change the specificity of 20 percent of the antigen receptors on B cells. The serum concentrations of the Ig isotypes are similar to those in nontransgenic littermates, but less than half of the serum IgM binds to NP, and none of the other isotypes do. Thus, neither network interactions nor random activation of a small fraction of the B cell population can account for serum Ig concentrations.

Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0670, USA.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Antibodies in a Heavy Chain Knock-In Mouse Exhibit Characteristics of Early Heavy Chain Rearrangement.
L. Yunk, W. Meng, P. L. Cohen, R. A. Eisenberg, and E. T. Luning Prak (2009)
J. Immunol. 183, 452-461
   Abstract »    Full Text »    PDF »
Two Distinct Populations of H Chain-Edited B Cells Show Differential Surrogate L Chain Dependence.
P. B. Nakajima, K. Kiefer, A. Price, G. C. Bosma, and M. J. Bosma (2009)
J. Immunol. 182, 3583-3596
   Abstract »    Full Text »    PDF »
Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching.
J. H. Wang, F. W. Alt, M. Gostissa, A. Datta, M. Murphy, M. B. Alimzhanov, K. M. Coakley, K. Rajewsky, J. P. Manis, and C. T. Yan (2008)
J. Exp. Med. 205, 3079-3090
   Abstract »    Full Text »    PDF »
An Activation-Induced Cytidine Deaminase-Independent Mechanism of Secondary VH Gene Rearrangement in Preimmune Human B Cells.
N. S. Longo, G. J. Grundy, J. Lee, M. Gellert, and P. E. Lipsky (2008)
J. Immunol. 181, 7825-7834
   Abstract »    Full Text »    PDF »
A Unique Role for the {lambda}5 Nonimmunoglobulin Tail in Early B Lymphocyte Development.
C. Vettermann, K. Herrmann, C. Albert, E. Roth, M. R. Bosl, and H.-M. Jack (2008)
J. Immunol. 181, 3232-3242
   Abstract »    Full Text »    PDF »
Requirements for the natural killer cell-mediated induction of IgG1 and IgG2a expression in B lymphocytes.
N. Gao, P. Jennings, and D. Yuan (2008)
Int. Immunol. 20, 645-657
   Abstract »    Full Text »    PDF »
CD22 Regulates Time Course of Both B Cell Division and Antibody Response.
T. Onodera, J. C. Poe, T. F. Tedder, and T. Tsubata (2008)
J. Immunol. 180, 907-913
   Abstract »    Full Text »    PDF »
Multiple, conserved cryptic recombination signals in VH gene segments: detection of cleavage products only in pro B cells.
M. Davila, F. Liu, L. G. Cowell, A. E. Lieberman, E. Heikamp, A. Patel, and G. Kelsoe (2007)
J. Exp. Med. 204, 3195-3208
   Abstract »    Full Text »    PDF »
TACI Is Required for Efficient Plasma Cell Differentiation in Response to T-Independent Type 2 Antigens.
G. T. Mantchev, C. S. Cortesao, M. Rebrovich, M. Cascalho, and R. J. Bram (2007)
J. Immunol. 179, 2282-2288
   Abstract »    Full Text »    PDF »
Ig Heavy Chain Promotes Mature B Cell Survival in the Absence of Light Chain.
P. Geraldes, M. Rebrovich, K. Herrmann, J. Wong, H.-M. Jack, M. Wabl, and M. Cascalho (2007)
J. Immunol. 179, 1659-1668
   Abstract »    Full Text »    PDF »
Salmonella Induces a Switched Antibody Response without Germinal Centers That Impedes the Extracellular Spread of Infection.
A. F. Cunningham, F. Gaspal, K. Serre, E. Mohr, I. R. Henderson, A. Scott-Tucker, S. M. Kenny, M. Khan, K.-M. Toellner, P. J. L. Lane, et al. (2007)
J. Immunol. 178, 6200-6207
   Abstract »    Full Text »    PDF »
Fitness of Cell-Mediated Immunity Independent of Repertoire Diversity.
M. AbuAttieh, M. Rebrovich, P. J. Wettstein, Z. Vuk-Pavlovic, A. H. Limper, J. L. Platt, and M. Cascalho (2007)
J. Immunol. 178, 2950-2960
   Abstract »    Full Text »    PDF »
Imprinting the Fate of Antigen-Reactive B Cells through the Affinity of the B Cell Receptor.
B. P. O'Connor, L. A. Vogel, W. Zhang, W. Loo, D. Shnider, E. F. Lind, M. Ratliff, R. J. Noelle, and L. D. Erickson (2006)
J. Immunol. 177, 7723-7732
   Abstract »    Full Text »    PDF »
VH Replacement Rescues Progenitor B Cells with Two Nonproductive VDJ Alleles.
J. Lutz, W. Muller, and H.-M. Jack (2006)
J. Immunol. 177, 7007-7014
   Abstract »    Full Text »    PDF »
Mechanisms of Neonatal Mucosal Antibody Protection.
N. L. Harris, I. Spoerri, J. F. Schopfer, C. Nembrini, P. Merky, J. Massacand, J. F. Urban Jr., A. Lamarre, K. Burki, B. Odermatt, et al. (2006)
J. Immunol. 177, 6256-6262
   Abstract »    Full Text »    PDF »
Establishment of Lymphotoxin beta Receptor Signaling-Dependent Cell Lines with Follicular Dendritic Cell Phenotypes from Mouse Lymph Nodes.
Y. Nishikawa, M. Hikida, M. Magari, N. Kanayama, M. Mori, H. Kitamura, T. Kurosaki, and H. Ohmori (2006)
J. Immunol. 177, 5204-5214
   Abstract »    Full Text »    PDF »
Characterization of (4-Hydroxy-3-Nitrophenyl)Acetyl (NP)-Specific Germinal Center B Cells and Antigen-Binding B220- Cells after Primary NP Challenge in Mice.
K. L. Wolniak, R. J. Noelle, and T. J. Waldschmidt (2006)
J. Immunol. 177, 2072-2079
   Abstract »    Full Text »    PDF »
B Cell Induction of IL-13 Expression in NK Cells: Role of CD244 and SLAM-Associated Protein..
N. Gao, P. Schwartzberg, J. A. Wilder, B. R. Blazar, and D. Yuan (2006)
J. Immunol. 176, 2758-2764
   Abstract »    Full Text »    PDF »
Receptors and Counterreceptors Involved in NK-B Cell Interactions.
N. Gao, T. Dang, W. A. Dunnick, J. T. Collins, B. R. Blazar, and D. Yuan (2005)
J. Immunol. 174, 4113-4119
   Abstract »    Full Text »    PDF »
Analysis of Marginal Zone B Cell Development in the Mouse with Limited B Cell Diversity: Role of the Antigen Receptor Signals in the Recruitment of B Cells to the Marginal Zone.
N. Kanayama, M. Cascalho, and H. Ohmori (2005)
J. Immunol. 174, 1438-1445
   Abstract »    Full Text »    PDF »
The Double-Edged Sword of Activation-Induced Cytidine Deaminase.
X. Wu, P. Geraldes, J. L. Platt, and M. Cascalho (2005)
J. Immunol. 174, 934-941
   Abstract »    Full Text »    PDF »
Receptor Editing in Positive and Negative Selection of B Lymphopoiesis.
E. Edry and D. Melamed (2004)
J. Immunol. 173, 4265-4271
   Abstract »    Full Text »    PDF »
B Cell-Dependent TCR Diversification.
C. Joao, B. M. Ogle, C. Gay-Rabinstein, J. L. Platt, and M. Cascalho (2004)
J. Immunol. 172, 4709-4716
   Abstract »    Full Text »    PDF »
Direct measurement of lymphocyte receptor diversity.
B. M. Ogle, M. Cascalho, C. Joao, W. Taylor, L. J. West, and J. L. Platt (2003)
Nucleic Acids Res. 31, e139
   Abstract »    Full Text »    PDF »
Antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies.
L. Hangartner, B. M. Senn, B. Ledermann, U. Kalinke, P. Seiler, E. Bucher, R. M. Zellweger, K. Fink, B. Odermatt, K. Burki, et al. (2003)
PNAS 100, 12883-12888
   Abstract »    Full Text »    PDF »
Receptor revision of immunoglobulin heavy chain genes in human MALT lymphomas.
D Lenze, A Greiner, C Knorr, I Anagnostopoulos, H Stein, and M Hummel (2003)
Mol. Pathol. 56, 249-255
   Abstract »    Full Text »    PDF »
Inhibitory Coreceptors Activated by Antigens But Not by Anti-Ig Heavy Chain Antibodies Install Requirement of Costimulation Through CD40 for Survival and Proliferation of B Cells.
Y. Hokazono, T. Adachi, M. Wabl, N. Tada, T. Amagasa, and T. Tsubata (2003)
J. Immunol. 171, 1835-1843
   Abstract »    Full Text »    PDF »
Antigen-capturing Cells Can Masquerade as Memory B Cells.
J. Bell and D. Gray (2003)
J. Exp. Med. 197, 1233-1244
   Abstract »    Full Text »    PDF »
B Cell Receptor-independent Stimuli Trigger Immunoglobulin (Ig) Class Switch Recombination and Production of IgG Autoantibodies by Anergic Self-Reactive B Cells.
T. G. Phan, M. Amesbury, S. Gardam, J. Crosbie, J. Hasbold, P. D. Hodgkin, A. Basten, and R. Brink (2003)
J. Exp. Med. 197, 845-860
   Abstract »    Full Text »    PDF »
B Cell Selection and Affinity Maturation During an Antibody Response in the Mouse with Limited B Cell Diversity.
N. Kanayama, T. Kimoto, K. Todo, Y. Nishikawa, M. Hikida, M. Magari, M. Cascalho, and H. Ohmori (2002)
J. Immunol. 169, 6865-6874
   Abstract »    Full Text »    PDF »
Short-lived and Long-lived Bone Marrow Plasma Cells Are Derived from a Novel Precursor Population.
B. P. O'Connor, M. Cascalho, and R. J. Noelle (2002)
J. Exp. Med. 195, 737-745
   Abstract »    Full Text »    PDF »
Low-level Hypermutation in T Cell-independent Germinal Centers Compared with High Mutation Rates Associated with T Cell-dependent Germinal Centers.
K.-M. Toellner, W. E. Jenkinson, D. R. Taylor, M. Khan, D. M.-Y. Sze, D. M. Sansom, C. G. Vinuesa, and I. C.M. MacLennan (2002)
J. Exp. Med. 195, 383-389
   Abstract »    Full Text »    PDF »
Lymphoid apoptosis and myeloid hyperplasia in CCAAT displacement protein mutant mice.
A. M. Sinclair, J. A. Lee, A. Goldstein, D. Xing, S. Liu, R. Ju, P. W. Tucker, E. J. Neufeld, and R. H. Scheuermann (2001)
Blood 98, 3658-3667
   Abstract »    Full Text »    PDF »
Development and Maintenance of a B220- Memory B Cell Compartment.
D. J. Driver, L. J. McHeyzer-Williams, M. Cool, D. B. Stetson, and M. G. McHeyzer-Williams (2001)
J. Immunol. 167, 1393-1405
   Abstract »    Full Text »    PDF »
Extrafollicular Plasmablast B Cells Play a Key Role in Carrying Retroviral Infection to Peripheral Organs.
D. Finke, F. Baribaud, H. Diggelmann, and H. Acha-Orbea (2001)
J. Immunol. 166, 6266-6275
   Abstract »    Full Text »    PDF »
VH Gene Replacement in Thymocytes.
R. Golub, D. Martin, F. E. Bertrand, M. Cascalho, M. Wabl, and G. E. Wu (2001)
J. Immunol. 166, 855-860
   Abstract »    Full Text »    PDF »
Intrinsic Constraint on Plasmablast Growth and Extrinsic Limits of Plasma Cell Survival.
D. M.-Y. Sze, K.-M. Toellner, C. G. de Vinuesa, D. R. Taylor, and I. C.M. MacLennan (2000)
J. Exp. Med. 192, 813-822
   Abstract »    Full Text »    PDF »
Stable and functional lymphoid reconstitution of common cytokine receptor gamma chain deficient mice by retroviral-mediated gene transfer.
C. Soudais, T. Shiho, L. I. Sharara, D. Guy-Grand, T. Taniguchi, A. Fischer, and J. P. Di Santo (2000)
Blood 95, 3071-3077
   Abstract »    Full Text »    PDF »
Antigen-Specific B Cell Memory: Expression and Replenishment of a Novel B220- Memory B Cell Compartment.
L. J. McHeyzer-Williams, M. Cool, and M. G. McHeyzer-Williams (2000)
J. Exp. Med. 191, 1149-1166
   Abstract »    Full Text »    PDF »
Affiliation to mature B cell repertoire and positive selection can be separated in two distinct processes.
S. Hachemi-Rachedi, A.-M. Drapier, P.-A. Cazenave, and P. Sanchez (2000)
Int. Immunol. 12, 385-395
   Abstract »    Full Text »    PDF »
Germinal Centers without T Cells.
C. G. de Vinuesa, M. C. Cook, J. Ball, M. Drew, Y. Sunners, M. Cascalho, M. Wabl, G. G.B. Klaus, and I. C.M. MacLennan (2000)
J. Exp. Med. 191, 485-494
   Abstract »    Full Text »    PDF »
A B220-, CD19- population of B cells in the peripheral blood of quasimonoclonal mice.
M. Cascalho, J. Wong, J. Brown, H.-M. Jack, C. Steinberg, and M. Wabl (2000)
Int. Immunol. 12, 29-35
   Abstract »    Full Text »    PDF »
B Cell Antigen Receptor Specificity and Surface Density Together Determine B-1 versus B-2 Cell Development.
K.-P. Lam and K. Rajewsky (1999)
J. Exp. Med. 190, 471-478
   Abstract »    Full Text »    PDF »
Secondary Rearrangements and Hypermutation Generate Sufficient B Cell Diversity to Mount Protective Antiviral Immunoglobulin Responses.
C. Lopez-Macias, U. Kalinke, M. Cascalho, M. Wabl, H. Hengartner, R. M. Zinkernagel, and A. Lamarre (1999)
J. Exp. Med. 189, 1791-1798
   Abstract »    Full Text »    PDF »
Transfer of Small Resting B Cells into Immunodeficient Hosts Results in the Selection of a Self-renewing Activated B Cell Population.
F. Agenes and A. A. Freitas (1999)
J. Exp. Med. 189, 319-330
   Abstract »    Full Text »    PDF »
B Cell Deletion, Anergy, and Receptor Editing in ""Knock In"" Mice Targeted with a Germline-Encoded or Somatically Mutated Anti-DNA Heavy Chain.
Y. Pewzner-Jung, D. Friedmann, E. Sonoda, S. Jung, K. Rajewsky, and D. Eilat (1998)
J. Immunol. 161, 4634-4645
   Abstract »    Full Text »    PDF »
V(D)J hypermutation and DNA mismatch repair: Vexed by fixation.
G. Kelsoe (1998)
PNAS 95, 6576-6577
   Full Text »    PDF »
Mismatch Repair Co-opted by Hypermutation.
M. Cascalho, J. Wong, C. Steinberg, and M. Wabl (1998)
Science 279, 1207-1210
   Abstract »    Full Text »


To Advertise     Find Products

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