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The Journal of Immunology, Vol 155, Issue 1 190-202, Copyright © 1995 by American Association of Immunologists


ARTICLES

Analysis of the heavy chain repertoire of human peripheral B cells using single-cell polymerase chain reaction

HP Brezinschek, RI Brezinschek and PE Lipsky
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235, USA.

The VH gene repertoire of human peripheral B cells was analyzed using PCR analysis of individual blood B cells. Because genomic DNA of single B cells was analyzed, data from both productive and nonproductive VDJ rearrangements were obtained. Nine out of 75 B cells contained both functional and nonfunctional rearrangement products, whereas 62/75 had a single productive VDJ rearrangement. The distribution of VH families was ordered in accordance with the germline complexity, although a bias toward VH3 and some of its members was found. This bias was noted in both the productively and nonproductively rearranged repertoires, indicating that it resulted from molecular and not selective processes. Evidence for negative selection of certain VH3 and VH4 family members was noted in that they were found less often as productive than nonproductive VDJ rearrangements. In addition, evidence for positive selection based on CDR3 was obtained, in that JH6 and DXP'1 were found at a higher frequency in the productively compared with the nonproductively rearranged repertoire. The CDR3 segments were markedly heterogenous, with a much greater degree of variability noted in the nonproductive VDJ rearrangements. Finally, a much greater frequency of mutations was noted in the nonproductively rearranged VH genes within individual B cells. These results have begun to delineate the human peripheral B cell repertoire and identify processes that shape it both positively and negatively.


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CVIHome page
D. Tewari
Clonal Analysis of the Human B-Cell Repertoire Using a Heteromobility Assay
Clin. Vaccine Immunol., May 1, 2000; 7(3): 507 - 509.
[Abstract] [Full Text] [PDF]


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BloodHome page
W. M. Aarts, R. J. Bende, E. J. Steenbergen, P. M. Kluin, E. C. M. Ooms, S. T. Pals, and C. J. M. van Noesel
Variable heavy chain gene analysis of follicular lymphomas: correlation between heavy chain isotype expression and somatic mutation load
Blood, May 1, 2000; 95(9): 2922 - 2929.
[Abstract] [Full Text] [PDF]


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NeurologyHome page
T. Smith-Jensen, M. P. Burgoon, J. Anthony, H. Kraus, D. H. Gilden, and G. P. Owens
Comparison of immunoglobulin G heavy-chain sequences in MS and SSPE brains reveals an antigen-driven response
Neurology, March 28, 2000; 54(6): 1227 - 1232.
[Abstract] [Full Text] [PDF]


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BloodHome page
I. S. Lossos, C. Y. Okada, R. Tibshirani, R. Warnke, J. M. Vose, T. C. Greiner, and R. Levy
Molecular analysis of immunoglobulin genes in diffuse large B-cell lymphomas
Blood, March 1, 2000; 95(5): 1797 - 1803.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
L. G. Cowell and T. B. Kepler
The Nucleotide-Replacement Spectrum Under Somatic Hypermutation Exhibits Microsequence Dependence That Is Strand-Symmetric and Distinct from That Under Germline Mutation
J. Immunol., February 15, 2000; 164(4): 1971 - 1976.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
D. K. Dunn-Walters, M. Hackett, L. Boursier, P. J. Ciclitira, P. Morgan, S. J. Challacombe, and J. Spencer
Characteristics of Human IgA and IgM Genes Used by Plasma Cells in the Salivary Gland Resemble Those Used in Duodenum But Not Those Used in the Spleen
J. Immunol., February 1, 2000; 164(3): 1595 - 1601.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
I. C. Nicholson, X. Zou, A. V. Popov, G. P. Cook, E. M. Corps, S. Humphries, C. Ayling, B. Goyenechea, J. Xian, M. J. Taussig, et al.
Antibody Repertoires of Four- and Five-Feature Translocus Mice Carrying Human Immunoglobulin Heavy Chain and {kappa} and {lambda} Light Chain Yeast Artificial Chromosomes
J. Immunol., December 15, 1999; 163(12): 6898 - 6906.
[Abstract] [Full Text] [PDF]


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Am. J. Pathol.Home page
M. Montesinos-Rongen, R. Kuppers, D. Schluter, T. Spieker, D. Van Roost, C. Schaller, G. Reifenberger, O. D. Wiestler, and M. Deckert-Schluter
Primary Central Nervous System Lymphomas Are Derived from Germinal-Center B Cells and Show a Preferential Usage of the V4-34 Gene Segment
Am. J. Pathol., December 1, 1999; 155(6): 2077 - 2086.
[Abstract] [Full Text] [PDF]


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NEJMHome page
R. Kuppers, U. Klein, M.-L. Hansmann, and K. Rajewsky
Cellular Origin of Human B-Cell Lymphomas
N. Engl. J. Med., November 11, 1999; 341(20): 1520 - 1529.
[Full Text] [PDF]


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J. Immunol.Home page
S. P. Rao, J. M. Riggs, D. F. Friedman, M. S. Scully, T. W. LeBien, and L. E. Silberstein
Biased VH Gene Usage in Early Lineage Human B Cells: Evidence for Preferential Ig Gene Rearrangement in the Absence of Selection
J. Immunol., September 1, 1999; 163(5): 2732 - 2740.
[Abstract] [Full Text] [PDF]


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BloodHome page
S. S. Sahota, R. Garand, R. Mahroof, A. Smith, N. Juge-Morineau, F. K. Stevenson, and R. Bataille
VH Gene Analysis of IgM-Secreting Myeloma Indicates an Origin From a Memory Cell Undergoing Isotype Switch Events
Blood, August 1, 1999; 94(3): 1070 - 1076.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
T. Dorner, N. L. Farner, and P. E. Lipsky
Ig {lambda} and Heavy Chain Gene Usage in Early Untreated Systemic Lupus Erythematosus Suggests Intensive B Cell Stimulation
J. Immunol., July 15, 1999; 163(2): 1027 - 1036.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
J. Spencer, M. Dunn, and D. K. Dunn-Walters
Characteristics of Sequences Around Individual Nucleotide Substitutions in IgVH Genes Suggest Different GC and AT Mutators
J. Immunol., June 1, 1999; 162(11): 6596 - 6601.
[Abstract] [Full Text] [PDF]


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Infect. Immun.Home page
L. Hougs, L. Juul, A. Svejgaard, and T. Barington
Structural Requirements of the Major Protective Antibody to Haemophilus influenzae Type b
Infect. Immun., May 1, 1999; 67(5): 2503 - 2514.
[Abstract] [Full Text] [PDF]


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GutHome page
D K Dunn-Walters, L Boursier, M Hackett, and J Spencer
Biased JH usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn's disease
Gut, March 1, 1999; 44(3): 382 - 386.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
H.-J. Kim, V. Krenn, G. Steinhauser, and C. Berek
Plasma Cell Development in Synovial Germinal Centers in Patients with Rheumatoid and Reactive Arthritis
J. Immunol., March 1, 1999; 162(5): 3053 - 3062.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
L. Hougs, L. Juul, H. J. Ditzel, C. Heilmann, A. Svejgaard, and T. Barington
The First Dose of a Haemophilus influenzae Type b Conjugate Vaccine Reactivates Memory B Cells: Evidence for Extensive Clonal Selection, Intraclonal Affinity Maturation, and Multiple Isotype Switches to IgA2
J. Immunol., January 1, 1999; 162(1): 224 - 237.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
S. Karray, L. Juompan, R. C. Maroun, D. Isenberg, G. J. Silverman, and M. Zouali
Structural Basis of the gp120 Superantigen-Binding Site on Human Immunoglobulins
J. Immunol., December 15, 1998; 161(12): 6681 - 6688.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
D. Sehgal, E. Schiaffella, A. O. Anderson, and R. G. Mage
Analyses of Single B Cells by Polymerase Chain Reaction Reveal Rearranged VH with Germline Sequences in Spleens of Immunized Adult Rabbits: Implications for B Cell Repertoire Maintenance and Renewal
J. Immunol., November 15, 1998; 161(10): 5347 - 5356.
[Abstract] [Full Text] [PDF]


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BloodHome page
W.M. Aarts, R. Willemze, R.J. Bende, C.J.L.M. Meijer, S.T. Pals, and C.J.M. van Noesel
VH Gene Analysis of Primary Cutaneous B-Cell Lymphomas: Evidence for Ongoing Somatic Hypermutation and Isotype Switching
Blood, November 15, 1998; 92(10): 3857 - 3864.
[Abstract] [Full Text] [PDF]


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JEMHome page
U. Klein, K. Rajewsky, and R. Kuppers
Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells
J. Exp. Med., November 2, 1998; 188(9): 1679 - 1689.
[Abstract] [Full Text] [PDF]


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BloodHome page
A. J. Szczepek, K. Seeberger, J. Wizniak, M. J. Mant, A. R. Belch, and L. M. Pilarski
A High Frequency of Circulating B Cells Share Clonotypic Ig Heavy-Chain VDJ Rearrangements With Autologous Bone Marrow Plasma Cells in Multiple Myeloma, as Measured by Single-Cell and In Situ Reverse Transcriptase-Polymerase Chain Reaction
Blood, October 15, 1998; 92(8): 2844 - 2855.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
R. Domiati-Saad and P. E. Lipsky
Staphylococcal Enterotoxin A Induces Survival of VH3-Expressing Human B Cells by Binding to the VH Region with Low Affinity
J. Immunol., August 1, 1998; 161(3): 1257 - 1266.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
H.-P. Brezinschek, S. J. Foster, T. Dorner, R. I. Brezinschek, and P. E. Lipsky
Pairing of Variable Heavy and Variable {kappa} Chains in Individual Naive and Memory B Cells
J. Immunol., May 15, 1998; 160(10): 4762 - 4767.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
E. A. Whitcomb and P. H. Brodeur
Rearrangement and Selection in the Developing V{kappa} Repertoire of the Mouse: An Analysis of the Usage of Two V{kappa} Gene Segments
J. Immunol., May 15, 1998; 160(10): 4904 - 4913.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
T. Dorner, H.-P. Brezinschek, S. J. Foster, R. I. Brezinschek, N. L. Farner, and P. E. Lipsky
Delineation of Selective Influences Shaping the Mutated Expressed Human Ig Heavy Chain Repertoire
J. Immunol., March 15, 1998; 160(6): 2831 - 2841.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
D. K. Dunn-Walters, A. Dogan, L. Boursier, C. M. MacDonald, and J. Spencer
Base-Specific Sequences That Bias Somatic Hypermutation Deduced by Analysis of Out-of-Frame Human IgVH Genes
J. Immunol., March 1, 1998; 160(5): 2360 - 2364.
[Abstract] [Full Text] [PDF]


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BloodHome page
G. Boucher, H. Broly, and R. Lemieux
Restricted Use of Cationic Germline VH Gene Segments in Human Rh(D) Red Cell Antibodies
Blood, May 1, 1997; 89(9): 3277 - 3286.
[Abstract] [Full Text] [PDF]


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BloodHome page
D. W. Bahler, J. A. Miklos, and S. H. Swerdlow
Ongoing Ig Gene Hypermutation in Salivary Gland Mucosa-Associated Lymphoid Tissue-Type Lymphomas
Blood, May 1, 1997; 89(9): 3335 - 3344.
[Abstract] [Full Text] [PDF]


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JEMHome page
L. Z. Rassenti and T. J. Kipps
Lack of Allelic Exclusion in B Cell Chronic Lymphocytic Leukemia
J. Exp. Med., April 21, 1997; 185(8): 1435 - 1446.
[Abstract] [Full Text] [PDF]




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