| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201; and
Department of Laboratory Medicine and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510
In the first week of the primary immune response to the
(4-hydroxy-3-nitrophenyl)acetyl (NP) hapten, plasmacytic foci and
germinal centers (GCs) in C57BL/6 mice are comprised of polyclonal
populations of B lymphocytes bearing the 
1 L-chain
(1+). The Ig H-chains of these early populations of B
cells are encoded by a variety of VH and D exons
undiversified by hypermutation while later, oligoclonal populations are
dominated by mutated rearrangements of the VH186.2 and
DFL16.1 gene segments. To assess directly Ab affinities within these
defined splenic microenvironments, representative VDJ rearrangements
were recovered from B cells participating in the early immune response
to NP, inserted into Ig H-chain expression cassettes, and transfected
into J558L (H-; 1+) myeloma cells. These
transfectoma Abs expressed a remarkably wide range of measured
affinities (Ka = 5 x
104-1.3 x 106 M-1) for NP.
VDJs recovered from both foci and early GCs generated comparable
affinities, suggesting that initial differentiation into these
compartments occurs stochastically. We conclude that Ag normally
activates B cells bearing an unexpectedly wide spectrum of Ab
affinities and that this initial, promiscuous clonal activation is
followed by affinity-driven competition to determine survival and
clonal expansion within GCs and entry into the memory and bone marrow
plasmacyte compartments.
This article has been cited by other articles:
|
|
 |
|
  S. M. Anderson, A. Khalil, M. Uduman, U. Hershberg, Y. Louzoun, A. M. Haberman, S. H. Kleinstein, and M. J. Shlomchik Taking Advantage: High-Affinity B Cells in the Germinal Center Have Lower Death Rates, but Similar Rates of Division, Compared to Low-Affinity Cells J. Immunol., December 1, 2009; 183(11): 7314 - 7325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kuraoka, D. Liao, K. Yang, S. D. Allgood, M. C. Levesque, G. Kelsoe, and Y. Ueda Activation-Induced Cytidine Deaminase Expression and Activity in the Absence of Germinal Centers: Insights into Hyper-IgM Syndrome J. Immunol., September 1, 2009; 183(5): 3237 - 3248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Eckl-Dorna and F. D. Batista BCR-mediated uptake of antigen linked to TLR9 ligand stimulates B-cell proliferation and antigen-specific plasma cell formation Blood, April 23, 2009; 113(17): 3969 - 3977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Luijkx, J. A. M. van Gaans-van den Brink, H. H. van Dijken, G. P. J. M. van den Dobbelsteen, and C. A. C. M. van Els Hyperproliferation of B Cells Specific for a Weakly Immunogenic PorA in a Meningococcal Vaccine Model Clin. Vaccine Immunol., October 1, 2008; 15(10): 1598 - 1605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. Sohn, P. Tolar, and S. K. Pierce Membrane heterogeneities in the formation of B cell receptor-Lyn kinase microclusters and the immune synapse J. Cell Biol., July 28, 2008; 182(2): 367 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Hershberg, M. Uduman, M. J. Shlomchik, and S. H. Kleinstein Improved methods for detecting selection by mutation analysis of Ig V region sequences Int. Immunol., May 1, 2008; 20(5): 683 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Gonzalez-Garcia, B. Rodriguez-Bayona, F. Mora-Lopez, A. Campos-Caro, and J. A. Brieva Increased survival is a selective feature of human circulating antigen-induced plasma cells synthesizing high-affinity antibodies Blood, January 15, 2008; 111(2): 741 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. DiLillo, Y. Hamaguchi, Y. Ueda, K. Yang, J. Uchida, K. M. Haas, G. Kelsoe, and T. F. Tedder Maintenance of Long-Lived Plasma Cells and Serological Memory Despite Mature and Memory B Cell Depletion during CD20 Immunotherapy in Mice J. Immunol., January 1, 2008; 180(1): 361 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Aviszus, X. Zhang, and L. J. Wysocki Silent Development of Memory Progenitor B Cells J. Immunol., October 15, 2007; 179(8): 5181 - 5190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ueda, D. Liao, K. Yang, A. Patel, and G. Kelsoe T-Independent Activation-Induced Cytidine Deaminase Expression, Class-Switch Recombination, and Antibody Production by Immature/Transitional 1 B Cells J. Immunol., March 15, 2007; 178(6): 3593 - 3601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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 Imprinting the Fate of Antigen-Reactive B Cells through the Affinity of the B Cell Receptor J. Immunol., December 1, 2006; 177(11): 7723 - 7732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Paus, T. G. Phan, T. D. Chan, S. Gardam, A. Basten, and R. Brink Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation J. Exp. Med., April 17, 2006; 203(4): 1081 - 1091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Han, X. Zhang, G. Wang, H. Guan, G. Garcia, P. Li, L. Feng, and B. Zheng FTY720 suppresses humoral immunity by inhibiting germinal center reaction Blood, December 15, 2004; 104(13): 4129 - 4133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Steeves and T. N. Marion Tolerance to DNA in (NZB x NZW)F1 Mice That Inherit an Anti-DNA VH as a Conventional {micro} H Chain Transgene but Not as a VH Knock-in Transgene J. Immunol., June 1, 2004; 172(11): 6568 - 6577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Han, E. Marinova, and B. Zheng Rectification of age-related impairment in Ig gene hypermutation during a memory response Int. Immunol., April 1, 2004; 16(4): 525 - 532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Zheng, E. Marinova, J. Han, T.-H. Tan, and S. Han Cutting Edge: {gamma}{delta} T Cells Provide Help to B Cells with Altered Clonotypes and Are Capable of Inducing Ig Gene Hypermutation J. Immunol., November 15, 2003; 171(10): 4979 - 4983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Han, K. Yang, Z. Ozen, W. Peng, E. Marinova, G. Kelsoe, and B. Zheng Enhanced Differentiation of Splenic Plasma Cells but Diminished Long-Lived High-Affinity Bone Marrow Plasma Cells in Aged Mice J. Immunol., February 1, 2003; 170(3): 1267 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kanayama, T. Kimoto, K. Todo, Y. Nishikawa, M. Hikida, M. Magari, M. Cascalho, and H. Ohmori B Cell Selection and Affinity Maturation During an Antibody Response in the Mouse with Limited B Cell Diversity J. Immunol., December 15, 2002; 169(12): 6865 - 6874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Inui, K. Maeda, D. R. Hua, T. Yamashita, H. Yamamoto, E. Miyamoto, S. Aizawa, and N. Sakaguchi BCR signal through {alpha}4 is involved in S6 kinase activation and required for B cell maturation including isotype switching and V region somatic hypermutation Int. Immunol., February 1, 2002; 14(2): 177 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-F. Lu, M. Singh, and J. Cerny Canonical germinal center B cells may not dominate the memory response to antigenic challenge Int. Immunol., May 1, 2001; 13(5): 643 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Hannum, A. M. Haberman, S. M. Anderson, and M. J. Shlomchik Germinal Center Initiation, Variable Gene Region Hypermutation, and Mutant B Cell Selection without Detectable Immune Complexes on Follicular Dendritic Cells J. Exp. Med., October 2, 2000; 192(7): 931 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Chen, S. B. Koralov, M. Gendelman, M. C. Carroll, and G. Kelsoe Humoral Immune Responses in Cr2-/- Mice: Enhanced Affinity Maturation but Impaired Antibody Persistence J. Immunol., May 1, 2000; 164(9): 4522 - 4532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Vora, K. Tumas-Brundage, and T. Manser Contrasting the In Situ Behavior of a Memory B Cell Clone During Primary and Secondary Immune Responses J. Immunol., October 15, 1999; 163(8): 4315 - 4327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Coffin, S. L. Clark, N. A. Bos, J. O. Brubaker, and P. A. Offit Migration of Antigen-Presenting B Cells from Peripheral to Mucosal Lymphoid Tissues May Induce Intestinal Antigen-Specific IgA Following Parenteral Immunization J. Immunol., September 15, 1999; 163(6): 3064 - 3070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kesmir and R. J. De Boer A Mathematical Model on Germinal Center Kinetics and Termination J. Immunol., September 1, 1999; 163(5): 2463 - 2469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takahashi, D. M. Cerasoli, J. M. Dal Porto, M. Shimoda, R. Freund, W. Fang, D. G. Telander, E.-N. Malvey, D. L. Mueller, T. W. Behrens, et al. Relaxed Negative Selection in Germinal Centers and Impaired Affinity Maturation in bcl-xL Transgenic Mice J. Exp. Med., August 2, 1999; 190(3): 399 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Dal Porto, A. M. Haberman, G. Kelsoe, and M. J. Shlomchik Very Low Affinity B Cells Form Germinal Centers, Become Memory B Cells, and Participate in Secondary Immune Responses When Higher Affinity Competition Is Reduced J. Exp. Med., May 6, 2002; 195(9): 1215 - 1221. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
