NDLI: Shaping of human germline IgH repertoires revealed by deep sequencing.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	McCormick, Michael W. Greenberg, Philip D. Larimore, Kevin Robins, Harlan S.
Description	Country affiliation: United States Author Affiliation: Larimore K ( Department of Immunology, University of Washington, Seattle, WA 98195, USA.)
Abstract	To understand better how selection processes balance the benefits of Ig repertoire diversity with the risks of autoreactivity and nonfunctionality of highly variable IgH CDR3s, we collected millions of rearranged germline IgH CDR3 sequences by deep sequencing of DNA from mature human naive B cells purified from four individuals and analyzed the data with computational methods. Long HCDR3 regions, often components of HIV-neutralizing Abs, appear to derive not only from incorporation of long D genes and insertion of large N regions but also by usage of multiple D gene segments in tandem. However, comparison of productive and out-of-frame IgH rearrangements revealed a selection bias against long HCDR3 loops, suggesting these may be disproportionately either poorly functional or autoreactive. Our data suggest that developmental selection removes HCDR3 loops containing patches of hydrophobicity, which are commonly found in some auto-antibodies, and at least 69% of the initial productive IgH rearrangements are removed from the repertoire during B cell development. Additionally, we have demonstrated the potential utility of this new technology for vaccine development with the identification in all four individuals of related candidate germline IgH precursors of the HIV-neutralizing Ab 4E10.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibodies, Neutralizing Biosynthesis B-lymphocyte Subsets Immunology Metabolism Gene Rearrangement, B-lymphocyte Immunoglobulin Heavy Chains Sequence Analysis, Dna Genetics Cytology Cell Differentiation Complementarity Determining Regions Computational Biology Conserved Sequence Hiv-1 Immunoglobulin Joining Region Immunoglobulin Variable Region Protein Precursors Somatic Hypermutation, Immunoglobulin Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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