| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
*
Division of Developmental and Clinical Immunology, Departments of
Medicine and
Microbiology, and
§
Specialized Center for Caries Research, University of Alabama, Birmingham, AL 35294
Due to the greater range of lengths available to the third complementarity determining region of the heavy chain (HCDR3), the Ab repertoire of normal adults includes larger Ag binding site structures than those seen in first and second trimester fetal tissues. Transition to a steady state range of HCDR3 lengths is not complete until the infant reaches 2 mo of age. Fetal constraints on length begin with a genetic predilection for use of short DH (D7-27 or DQ52) gene segments and against use of long DH (e.g., D3 or DXP) and JH (JH6) gene segments in both fetal liver and fetal bone marrow. Further control of length is achieved through DH-specific limitations in N addition, with D7-27 DJ joins including extensive N addition and D3-containing DJ joins showing a paucity of N addition. DH-specific constraints on N addition are no longer apparent in adult bone marrow. Superimposed upon these genetic mechanisms to control length is a process of somatic selection that appears to ensure expression of a restricted range of HCDR3 lengths in both fetus and adult. B cells that express Abs of an "inappropriate" length appear to be eliminated when they first display IgM on their cell surface. Control of N addition appears aberrant in X-linked agammaglobulinemia, which may exacerbate the block in B cell development seen in this disease. Restriction of the fetal repertoire appears to be an active process, forcing limits on the diversity, and hence range of Ab specificities, available to the young.
This article has been cited by other articles:
|
|
 |
|
  M. Zemlin, G. Hoersch, C. Zemlin, A. Pohl-Schickinger, M. Hummel, C. Berek, R. F. Maier, and K. Bauer The Postnatal Maturation of the Immunoglobulin Heavy Chain IgG Repertoire in Human Preterm Neonates Is Slower than in Term Neonates J. Immunol., January 15, 2007; 178(2): 1180 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Souto-Carneiro, G. P. Sims, H. Girschik, J. Lee, and P. E. Lipsky Developmental Changes in the Human Heavy Chain CDR3 J. Immunol., December 1, 2005; 175(11): 7425 - 7436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Schelonka, I. I. Ivanov, D. H. Jung, G. C. Ippolito, L. Nitschke, Y. Zhuang, G. L. Gartland, J. Pelkonen, F. W. Alt, K. Rajewsky, et al. A Single DH Gene Segment Creates Its Own Unique CDR-H3 Repertoire and Is Sufficient for B cell Development and Immune Function J. Immunol., November 15, 2005; 175(10): 6624 - 6632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Stamatopoulos, C. Belessi, A. Hadzidimitriou, T. Smilevska, E. Kalagiakou, K. Hatzi, N. Stavroyianni, A. Athanasiadou, A. Tsompanakou, T. Papadaki, et al. Immunoglobulin light chain repertoire in chronic lymphocytic leukemia Blood, November 15, 2005; 106(10): 3575 - 3583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. I. Ivanov, R. L. Schelonka, Y. Zhuang, G. L. Gartland, M. Zemlin, and H. W. Schroeder Jr. Development of the Expressed Ig CDR-H3 Repertoire Is Marked by Focusing of Constraints in Length, Amino Acid Use, and Charge That Are First Established in Early B Cell Progenitors J. Immunol., June 15, 2005; 174(12): 7773 - 7780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yurasov, H. Wardemann, J. Hammersen, M. Tsuiji, E. Meffre, V. Pascual, and M. C. Nussenzweig Defective B cell tolerance checkpoints in systemic lupus erythematosus J. Exp. Med., March 7, 2005; 201(5): 703 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Kolar, T. Yokota, M. I. D. Rossi, S. K. Nath, and J. D. Capra Human fetal, cord blood, and adult lymphocyte progenitors have similar potential for generating B cells with a diverse immunoglobulin repertoire Blood, November 1, 2004; 104(9): 2981 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-S. Ng, H. Wardemann, J. Chelnis, C. Cunningham-Rundles, and E. Meffre Bruton's Tyrosine Kinase Is Essential for Human B Cell Tolerance J. Exp. Med., October 4, 2004; 200(7): 927 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wardemann, J. Hammersen, and M. C. Nussenzweig Human Autoantibody Silencing by Immunoglobulin Light Chains J. Exp. Med., July 19, 2004; 200(2): 191 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Souto-Carneiro, N. S. Longo, D. E. Russ, H.-w. Sun, and P. E. Lipsky Characterization of the Human Ig Heavy Chain Antigen Binding Complementarity Determining Region 3 Using a Newly Developed Software Algorithm, JOINSOLVER J. Immunol., June 1, 2004; 172(11): 6790 - 6802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Martin, H. Bradl, T. J. Collins, E. Roth, H.-M. Jack, and G. E. Wu Selection of Ig {micro} Heavy Chains by Complementarity-Determining Region 3 Length and Amino Acid Composition J. Immunol., November 1, 2003; 171(9): 4663 - 4671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Weitkamp, N. Kallewaard, K. Kusuhara, E. Bures, J. V. Williams, B. LaFleur, H. B. Greenberg, and J. E. Crowe Jr. Infant and Adult Human B Cell Responses to Rotavirus Share Common Immunodominant Variable Gene Repertoires J. Immunol., November 1, 2003; 171(9): 4680 - 4688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wardemann, S. Yurasov, A. Schaefer, J. W. Young, E. Meffre, and M. C. Nussenzweig Predominant Autoantibody Production by Early Human B Cell Precursors Science, September 5, 2003; 301(5638): 1374 - 1377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G R Kolar and J D Capra The NOD/SCID chimeric mouse model of human B cell development: studies on the VH4 family immunoglobulin repertoire and implications for SLE Lupus, March 1, 2003; 12(3): 158 - 162. [Abstract] [PDF]
|
|
|
|
 |
|
 J. L. Wiemels, B. C. Leonard, Y. Wang, M. R. Segal, S. P. Hunger, M. T. Smith, V. Crouse, X. Ma, P. A. Buffler, and S. R. Pine Site-specific translocation and evidence of postnatal origin of the t(1;19) E2A-PBX1 fusion in childhood acute lymphoblastic leukemia PNAS, November 12, 2002; 99(23): 15101 - 15106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
F. E. Bertrand, C. Vogtenhuber, N. Shah, and T. W. LeBien Pro-B-cell to pre-B-cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein Blood, December 1, 2001; 98(12): 3398 - 3405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Schroeder Jr, L. Zhang, and J. B. Philips III Slow, programmed maturation of the immunoglobulin HCDR3 repertoire during the third trimester of fetal life Blood, November 1, 2001; 98(9): 2745 - 2751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. D. Rossi, K. L. Medina, K. Garrett, G. Kolar, P. C. Comp, L. D. Shultz, J. D. Capra, P. Wilson, A. Schipul, and P. W. Kincade Relatively Normal Human Lymphopoiesis but Rapid Turnover of Newly Formed B Cells in Transplanted Nonobese Diabetic/SCID Mice J. Immunol., September 15, 2001; 167(6): 3033 - 3042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zemlin, K. Bauer, M. Hummel, S. Pfeiffer, S. Devers, C. Zemlin, H. Stein, and H. T. Versmold The diversity of rearranged immunoglobulin heavy chain variable region genes in peripheral blood B cells of preterm infants is restricted by short third complementarity-determining regions but not by limited gene segment usage Blood, March 1, 2001; 97(5): 1511 - 1513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Nitschke, J. Kestler, T. Tallone, S. Pelkonen, and J. Pelkonen Deletion of the DQ52 Element Within the Ig Heavy Chain Locus Leads to a Selective Reduction in VDJ Recombination and Altered D Gene Usage J. Immunol., February 15, 2001; 166(4): 2540 - 2552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Butler, P. Weber, M. Sinkora, J. Sun, S. J. Ford, and R. K. Christenson Antibody Repertoire Development in Fetal and Neonatal Piglets. II. Characterization of Heavy Chain Complementarity-Determining Region 3 Diversity in the Developing Fetus J. Immunol., December 15, 2000; 165(12): 6999 - 7010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lee, N. L. Monson, and P. E. Lipsky The V{lambda}J{lambda} Repertoire in Human Fetal Spleen: Evidence for Positive Selection and Extensive Receptor Editing J. Immunol., December 1, 2000; 165(11): 6322 - 6333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. LeBien Fates of human B-cell precursors Blood, July 1, 2000; 96(1): 9 - 23. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
