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Regulation of Repertoire Development through Genetic Control of D(H) Reading Frame Preference

Zemlin M, Schelonka RL, Ippolito GC, Zemlin C, Zhuang Y, Gartland GL, Nitschke L, Pelkonen J, Rajewsky K, Schroeder HW (2008)

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Publication Status: Published

Publication Type: Journal article

Publication year: 2008

Journal

Publisher: AMER ASSOC IMMUNOLOGISTS

Book Volume: 181

Pages Range: 8416-8424

Journal Issue: 12

Abstract

In jawed vertebrates most expressed Ig H chains use only one of six possible D, reading frames. Reading frame (RF)1, the preferred reading frame, tends to encode tyrosine and glycine, whereas the other five RFs tend to be enriched for either hydrophobic or charged amino acids. Mechanisms proposed to favor use of RF1 include a preference for deletion over inversion that discourages use of inverted RF1, RF2, and RF3; sequence homology between the 5' terminus of the J(H) and the 3' terminus of the D(H) that promotes rearrangement into RF1; an ATG start site upstream of RF2 that permits production of a truncated D mu protein; stop codons in RF3; and, following surface expression of IgM, somatic, presumably Ag receptor-based selection favoring B cells expressing Igs with tyrosine- and glycine-enriched CDR-H3s. By creating an IgH allele limited to the use of a single, frameshifted DFL16.1 D(H) gene segment, we tested the relative contribution of these mechanisms in determining reading frame preference. D mu-mediated suppression via an allelic exclusion-like mechanism dominated over somatic selection in determining the composition of the CDR-H3 repertoire. Evidence of somatic selection for RF1-encoded tyrosine in CDR-H3 was observed, but only among the minority of recirculating, mature B cells that use D(H) in RF1. These observations underscore the extent to which the sequence of the D(H) acts to delimit the diversity of the Ab repertoire. The Journal of Immunology, 2008, 181: 8416-8424.

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How to cite

APA:

Zemlin, M., Schelonka, R.L., Ippolito, G.C., Zemlin, C., Zhuang, Y., Gartland, G.L.,... Schroeder, H.W. (2008). Regulation of Repertoire Development through Genetic Control of D(H) Reading Frame Preference. Journal of Immunology, 181(12), 8416-8424.

MLA:

Zemlin, Michael, et al. "Regulation of Repertoire Development through Genetic Control of D(H) Reading Frame Preference." Journal of Immunology 181.12 (2008): 8416-8424.

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