Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Klein, U.
Right arrow Articles by Rajewsky, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Klein, U.
Right arrow Articles by Rajewsky, K.
Related Collections
Right arrow Immunobiology
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

Evidence for a large compartment of IgM-expressing memory B cells in humans

U Klein, R Kuppers and K Rajewsky

Institute for Genetics, University of Cologne, Germany.

The recent finding of somatically mutated mu heavy chain transcripts in human peripheral blood (PB) B lymphocytes suggests that T-dependent B- cell memory might not be restricted to class-switched cells. We provide here evidence that IgM-only PB B cells are likely to be the IgM- expressing counterpart of classical (IgM- IgD-) memory B cells in humans. As shown by molecular single cell analysis, most IgM-only cells carry mutated V region genes, like class-switched cells. Although both subsets represent populations of nonactivated, resting cells, they express higher levels of Ig mRNA than naive (IgM+ IgD+) B cells. IgM- only and class-switched cells are CD38- CD77-, and mostly CD23-, thus neither resembling germinal center nor naive B cells. Because many IgM- expressing B cells located in secondary lymphoid tissues resemble IgM- only PB B cells in terms of cell phenotype, we propose that the human lymphoid system contains a large compartment of IgM-expressing memory cells. Moreover, these cells seem to represent the nonmalignant counterparts of IgM-expressing tumor cells in sporadic Burkitt's lymphoma, MALT lymphoma, monocytoid B-cell lymphoma, and diffuse large- cell lymphoma that were found to harbor somatically mutated V genes.

Volume 89, Issue 4, pp. 1288-1298, 02/15/1997
Copyright © 1997 by The American Society of Hematology


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
J. Immunol.Home page
M. M. Tomayko, S. M. Anderson, C. E. Brayton, S. Sadanand, N. C. Steinel, T. W. Behrens, and M. J. Shlomchik
Systematic Comparison of Gene Expression between Murine Memory and Naive B Cells Demonstrates That Memory B Cells Have Unique Signaling Capabilities
J. Immunol., July 1, 2008; 181(1): 27 - 38.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Med.Home page
S. Weller, M. Mamani-Matsuda, C. Picard, C. Cordier, D. Lecoeuche, F. Gauthier, J.-C. Weill, and C.-A. Reynaud
Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants
J. Exp. Med., June 9, 2008; 205(6): 1331 - 1342.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
E. D. Charles, R. M. Green, S. Marukian, A. H. Talal, G. V. Lake-Bakaar, I. M. Jacobson, C. M. Rice, and L. B. Dustin
Clonal expansion of immunoglobulin M+CD27+ B cells in HCV-associated mixed cryoglobulinemia
Blood, February 1, 2008; 111(3): 1344 - 1356.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
F. Capolunghi, S. Cascioli, E. Giorda, M. M. Rosado, A. Plebani, C. Auriti, G. Seganti, R. Zuntini, S. Ferrari, M. Cagliuso, et al.
CpG Drives Human Transitional B Cells to Terminal Differentiation and Production of Natural Antibodies
J. Immunol., January 15, 2008; 180(2): 800 - 808.
[Abstract] [Full Text] [PDF]


Home page
Int ImmunolHome page
A. Lim, B. Lemercier, X. Wertz, S. L. Pottier, F. Huetz, and P. Kourilsky
Many human peripheral VH5-expressing IgM+ B cells display a unique heavy-chain rearrangement
Int. Immunol., January 1, 2008; 20(1): 105 - 116.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Med.Home page
S. M. Anderson, M. M. Tomayko, A. Ahuja, A. M. Haberman, and M. J. Shlomchik
New markers for murine memory B cells that define mutated and unmutated subsets
J. Exp. Med., September 3, 2007; 204(9): 2103 - 2114.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
S. G. Tangye and K. L. Good
Human IgM+CD27+ B Cells: Memory B Cells or "Memory" B Cells?
J. Immunol., July 1, 2007; 179(1): 13 - 19.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
J. F. Fecteau, G. Cote, and S. Neron
A New Memory CD27-IgG+ B Cell Population in Peripheral Blood Expressing VH Genes with Low Frequency of Somatic Mutation
J. Immunol., September 15, 2006; 177(6): 3728 - 3736.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
S. Casola, G. Cattoretti, N. Uyttersprot, S. B. Koralov, J. Segal, Z. Hao, A. Waisman, A. Egert, D. Ghitza, and K. Rajewsky
Tracking germinal center B cells expressing germ-line immunoglobulin {gamma}1 transcripts by conditional gene targeting
PNAS, May 9, 2006; 103(19): 7396 - 7401.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
D. Bechtel, J. Kurth, C. Unkel, and R. Kuppers
Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas
Blood, December 15, 2005; 106(13): 4345 - 4350.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
T. A. Souza, B. D. Stollar, J. L. Sullivan, K. Luzuriaga, and D. A. Thorley-Lawson
Peripheral B cells latently infected with Epstein-Barr virus display molecular hallmarks of classical antigen-selected memory B cells
PNAS, December 13, 2005; 102(50): 18093 - 18098.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
M. Montesinos-Rongen, R. Schmitz, C. Courts, W. Stenzel, D. Bechtel, G. Niedobitek, I. Blumcke, G. Reifenberger, A. von Deimling, B. Jungnickel, et al.
Absence of Immunoglobulin Class Switch in Primary Lymphomas of the Central Nervous System
Am. J. Pathol., June 1, 2005; 166(6): 1773 - 1779.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
M. Carbonari, E. Caprini, T. Tedesco, F. Mazzetta, V. Tocco, M. Casato, G. Russo, and M. Fiorilli
Hepatitis C Virus Drives the Unconstrained Monoclonal Expansion of VH1-69-Expressing Memory B Cells in Type II Cryoglobulinemia: A Model of Infection-Driven Lymphomagenesis
J. Immunol., May 15, 2005; 174(10): 6532 - 6539.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
D. C. Macallan, D. L. Wallace, Y. Zhang, H. Ghattas, B. Asquith, C. de Lara, A. Worth, G. Panayiotakopoulos, G. E. Griffin, D. F. Tough, et al.
B-cell kinetics in humans: rapid turnover of peripheral blood memory cells
Blood, May 1, 2005; 105(9): 3633 - 3640.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. Weller, M. C. Braun, B. K. Tan, A. Rosenwald, C. Cordier, M. E. Conley, A. Plebani, D. S. Kumararatne, D. Bonnet, O. Tournilhac, et al.
Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire
Blood, December 1, 2004; 104(12): 3647 - 3654.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
M. C. Jaimes, O. L. Rojas, E. J. Kunkel, N. H. Lazarus, D. Soler, E. C. Butcher, D. Bass, J. Angel, M. A. Franco, and H. B. Greenberg
Maturation and Trafficking Markers on Rotavirus-Specific B Cells during Acute Infection and Convalescence in Children
J. Virol., October 15, 2004; 78(20): 10967 - 10976.
[Abstract] [Full Text] [PDF]


Home page
LupusHome page
T Dorner and P E Lipsky
Correlation of circulating CD27high plasma cells and disease activity in systemic lupus erythematosus
Lupus, May 1, 2004; 13(5): 283 - 289.
[Abstract] [PDF]


Home page
J. Gen. Virol.Home page
J. O'Nions and M. J. Allday
Proliferation and differentiation in isogenic populations of peripheral B cells activated by Epstein-Barr virus or T cell-derived mitogens
J. Gen. Virol., April 1, 2004; 85(4): 881 - 895.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
G. Kennedy, J. Komano, and B. Sugden
Epstein-Barr virus provides a survival factor to Burkitt's lymphomas
PNAS, November 25, 2003; 100(24): 14269 - 14274.
[Abstract] [Full Text] [PDF]


Home page
Ann Rheum DisHome page
M Odendahl, R Keitzer, U Wahn, F Hiepe, A Radbruch, T Dorner, and R Bunikowski
Perturbations of peripheral B lymphocyte homoeostasis in children with systemic lupus erythematosus
Ann Rheum Dis, September 1, 2003; 62(9): 851 - 858.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Med.Home page
K. A. Pape, V. Kouskoff, D. Nemazee, H. L. Tang, J. G. Cyster, L. E. Tze, K. L. Hippen, T. W. Behrens, and M. K. Jenkins
Visualization of the Genesis and Fate of Isotype-switched B Cells during a Primary Immune Response
J. Exp. Med., June 16, 2003; 197(12): 1677 - 1687.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
N. L. Bernasconi, N. Onai, and A. Lanzavecchia
A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells
Blood, June 1, 2003; 101(11): 4500 - 4504.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
S. G. Tangye, D. T. Avery, E. K. Deenick, and P. D. Hodgkin
Intrinsic Differences in the Proliferation of Naive and Memory Human B Cells as a Mechanism for Enhanced Secondary Immune Responses
J. Immunol., January 15, 2003; 170(2): 686 - 694.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Med.Home page
N. Feldhahn, I. Schwering, S. Lee, M. Wartenberg, F. Klein, H. Wang, G. Zhou, S. M. Wang, J. D. Rowley, J. Hescheler, et al.
Silencing of B Cell Receptor Signals in Human Naive B Cells
J. Exp. Med., November 18, 2002; 196(10): 1291 - 1305.
[Abstract] [Full Text] [PDF]


Home page
J. Gerontol. A Biol. Sci. Med. Sci.Home page
E. Breitbart, X. Wang, L. S. Leka, G. E. Dallal, S. N. Meydani, and B. D. Stollar
Altered Memory B-Cell Homeostasis in Human Aging
J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2002; 57(8): B304 - 311.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
K. Bauer, M. Zemlin, M. Hummel, S. Pfeiffer, J. Karstaedt, G. Steinhauser, X. Xiao, H. Versmold, and C. Berek
Diversification of Ig Heavy Chain Genes in Human Preterm Neonates Prematurely Exposed to Environmental Antigens
J. Immunol., August 1, 2002; 169(3): 1349 - 1356.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
K. Warnatz, A. Denz, R. Drager, M. Braun, C. Groth, G. Wolff-Vorbeck, H. Eibel, M. Schlesier, and H. H. Peter
Severe deficiency of switched memory B cells (CD27+IgM-IgD-) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease
Blood, March 1, 2002; 99(5): 1544 - 1551.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
P. Algara, M. S. Mateo, M. Sanchez-Beato, M. Mollejo, I. C. Navas, L. Romero, F. Sole, M. Salido, L. Florensa, P. Martinez, et al.
Analysis of the IgVH somatic mutations in splenic marginal zone lymphoma defines a group of unmutated cases with frequent 7q deletion and adverse clinical course
Blood, February 15, 2002; 99(4): 1299 - 1304.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
I. R. Blanca, E. W. Bere, H. A. Young, and J. R. Ortaldo
Human B Cell Activation by Autologous NK Cells Is Regulated by CD40-CD40 Ligand Interaction: Role of Memory B Cells and CD5+ B Cells
J. Immunol., December 1, 2001; 167(11): 6132 - 6139.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
M. B. Bjorgan, J. E. Thoen, J. B. Natvig, and K. M. Thompson
Bm1-Bm5 Classification of Peripheral Blood B Cells Reveals Circulating Germinal Center Founder Cells in Healthy Individuals and Disturbance in the B Cell Subpopulations in Patients with Primary Sjogren's Syndrome
J. Immunol., October 1, 2001; 167(7): 3610 - 3618.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
F. Forconi, S. S. Sahota, D. Raspadori, C. I. Mockridge, F. Lauria, and F. K. Stevenson
Tumor cells of hairy cell leukemia express multiple clonally related immunoglobulin isotypes via RNA splicing
Blood, August 15, 2001; 98(4): 1174 - 1181.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
R. Marzari, D. Sblattero, F. Florian, E. Tongiorgi, T. Not, A. Tommasini, A. Ventura, and A. Bradbury
Molecular Dissection of the Tissue Transglutaminase Autoantibody Response in Celiac Disease
J. Immunol., March 15, 2001; 166(6): 4170 - 4176.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
S. Weller, A. Faili, C. Garcia, M. C. Braun, F. Le Deist, G. de Saint Basile, O. Hermine, A. Fischer, C.-A. Reynaud, and J.-C. Weill
CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans
PNAS, January 30, 2001; 98(3): 1166 - 1170.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
M. Odendahl, A. Jacobi, A. Hansen, E. Feist, F. Hiepe, G. R. Burmester, P. E. Lipsky, A. Radbruch, and T. Dorner
Disturbed Peripheral B Lymphocyte Homeostasis in Systemic Lupus Erythematosus
J. Immunol., November 15, 2000; 165(10): 5970 - 5979.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
S. J. Richards, G. J. Morgan, and P. Hillmen
Immunophenotypic analysis of B cells in PNH: insights into the generation of circulating naive and memory B cells
Blood, November 15, 2000; 96(10): 3522 - 3528.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
A. M. Joseph, G. J. Babcock, and D. A. Thorley-Lawson
EBV Persistence Involves Strict Selection of Latently Infected B Cells
J. Immunol., September 15, 2000; 165(6): 2975 - 2981.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Med.Home page
H. White and D. Gray
Analysis of Immunoglobulin (Ig) Isotype Diversity and IgM/D Memory in the Response to Phenyl-Oxazolone
J. Exp. Med., June 19, 2000; 191(12): 2209 - 2220.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
M. Dono, S. Zupo, N. Leanza, G. Melioli, M. Fogli, A. Melagrana, N. Chiorazzi, and M. Ferrarini
Heterogeneity of Tonsillar Subepithelial B Lymphocytes, the Splenic Marginal Zone Equivalents
J. Immunol., June 1, 2000; 164(11): 5596 - 5604.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
S. M. Shinall, M. Gonzalez-Fernandez, R. J. Noelle, and T. J. Waldschmidt
Identification of Murine Germinal Center B Cell Subsets Defined by the Expression of Surface Isotypes and Differentiation Antigens
J. Immunol., June 1, 2000; 164(11): 5729 - 5738.
[Abstract] [Full Text] [PDF]


Home page
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]


Home page
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]


Home page
J. Biol. Chem.Home page
H. J. de Haard, N. van Neer, A. Reurs, S. E. Hufton, R. C. Roovers, P. Henderikx, A. P. de Bruine, J.-W. Arends, and H. R. Hoogenboom
A Large Non-immunized Human Fab Fragment Phage Library That Permits Rapid Isolation and Kinetic Analysis of High Affinity Antibodies
J. Biol. Chem., June 25, 1999; 274(26): 18218 - 18230.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Tierens, J. Delabie, L. Michiels, P. Vandenberghe, and C. De Wolf-Peeters
Marginal-Zone B Cells in the Human Lymph Node and Spleen Show Somatic Hypermutations and Display Clonal Expansion
Blood, January 1, 1999; 93(1): 226 - 234.
[Abstract] [Full Text] [PDF]

<