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Department of Microbiology and Iowa Interdisciplinary Immunology Program, University of Iowa, Iowa City, IA 52242;
Department of Animal Science, Iowa State University, Ames, IA 52242; and
U.S. Department of Agriculture, Agricultural Research Service, Roman L. Hruska U.S. Meat Animal Research Center, Clay Center, NE 68933
Since the actual combinatorial diversity in the VH repertoire in fetal piglets represents <1% of the potential in mice and humans, we wondered whether 1) complementarity-determining region 3 (CDR3) diversity was also restricted; 2) CDR3 diversity changed with fetal age; and 3) to what extent CDR3 contributed to the preimmune VDJ repertoire. CDR3 spectratyping and sequence analyses of 213 CDR3s recovered from >30 fetal animals of different ages showed that >95% of VDJ diversity resulted from junctional diversity. Unlike sheep and cattle, somatic hypermutation does not contribute to the repertoire. These studies also revealed that 1) N region additions are as extensive in VDJ rearrangements recovered at 30 days as those in late term fetuses, suggesting that TdT is fully active at the onset of VDJ rearrangement; 2) nearly 90% of all rearrangement are in-frame until late gestation; 3) the oligoclonal CDR3 spectratype of 30-day fetal liver becomes polyclonal by 50 days, while this change occurs much later in spleen; 4) there is little evidence of individual variation in CDR3 spectratype or differences in spectratype among lymphoid tissues with the exception of the thymus; and 4) there is a tendency for usage of the most JH proximal DH segment (DHB) to decrease in older fetuses and for the longer DH segment to be trimmed to the same length as the shorter DH when used in CDR3. These findings suggest that in the fetal piglet, highly restricted combinatorial diversity and the lack of somatic mutation are compensated by early onset of TdT activity and other mechanisms that contribute to CDR3 junctional diversity.
This article has been cited by other articles:
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  J. E. Butler, N. Wertz, P. Weber, and K. M. Lager Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3 J. Immunol., February 15, 2008; 180(4): 2347 - 2356. [Abstract] [Full Text] [PDF]
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J. E. Butler, C. D. Lemke, P. Weber, M. Sinkora, and K. M. Lager Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome J. Immunol., May 15, 2007; 178(10): 6320 - 6331. [Abstract] [Full Text] [PDF]
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J. E. Butler, P. Weber, and N. Wertz Antibody Repertoire Development in Fetal and Neonatal Piglets. XIII. Hybrid VH Genes and the Preimmune Repertoire Revisited J. Immunol., October 15, 2006; 177(8): 5459 - 5470. [Abstract] [Full Text] [PDF]
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J. E. Butler and N. Wertz Antibody Repertoire Development in Fetal and Neonatal Piglets. XVII. IgG Subclass Transcription Revisited with Emphasis on New IgG3 J. Immunol., October 15, 2006; 177(8): 5480 - 5489. [Abstract] [Full Text] [PDF]
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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]
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J. E. Butler, D. H. Francis, J. Freeling, P. Weber, and A. M. Krieg Antibody Repertoire Development in Fetal and Neonatal Piglets. IX. Three Pathogen-Associated Molecular Patterns Act Synergistically to Allow Germfree Piglets to Respond to Type 2 Thymus-Independent and Thymus-Dependent Antigens J. Immunol., November 15, 2005; 175(10): 6772 - 6785. [Abstract] [Full Text] [PDF]
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J. E. Butler, N. Wertz, J. Sun, H. Wang, P. Chardon, F. Piumi, and K. Wells Antibody Repertoire Development in Fetal and Neonatal Pigs. VII. Characterization of the Preimmune {kappa} Light Chain Repertoire J. Immunol., December 1, 2004; 173(11): 6794 - 6805. [Abstract] [Full Text] [PDF]
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M. Sinkora, J. Sun, J. Sinkorova, R. K. Christenson, S. P. Ford, and J. E. Butler Antibody Repertoire Development in Fetal and Neonatal Piglets. VI. B Cell Lymphogenesis Occurs at Multiple Sites with Differences in the Frequency of In-frame Rearrangements J. Immunol., February 15, 2003; 170(4): 1781 - 1788. [Abstract] [Full Text] [PDF]
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J. E. Butler, P. Weber, M. Sinkora, D. Baker, A. Schoenherr, B. Mayer, and D. Francis Antibody Repertoire Development in Fetal and Neonatal Piglets. VIII. Colonization Is Required for Newborn Piglets to Make Serum Antibodies to T-Dependent and Type 2 T-Independent Antigens J. Immunol., December 15, 2002; 169(12): 6822 - 6830. [Abstract] [Full Text] [PDF]
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J. E. Butler, J. Sun, P. Weber, S. P. Ford, Z. Rehakova, J. Sinkora, and K. Lager Antibody Repertoire Development in Fetal And Neonatal Piglets. IV. Switch Recombination, Primarily in Fetal Thymus, Occurs Independent of Environmental Antigen and Is Only Weakly Associated with Repertoire Diversification J. Immunol., September 15, 2001; 167(6): 3239 - 3249. [Abstract] [Full Text] [PDF]
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