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Immunoglobulin heavy chain expression shapes the B cell receptor repertoire in human B cell development
Eric Meffre, … , Michel C. Nussenzweig, Claudine Schiff
Eric Meffre, … , Michel C. Nussenzweig, Claudine Schiff
Published September 15, 2001
Citation Information: J Clin Invest. 2001;108(6):879-886. https://doi.org/10.1172/JCI13051.
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Immunoglobulin heavy chain expression shapes the B cell receptor repertoire in human B cell development

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Abstract

Developing B cells must pass a series of checkpoints that are regulated by membrane-bound Igμ through the Igα-Igβ signal transducers. To determine how Igμ expression affects B cell development and Ab selection in humans we analyzed Ig gene rearrangements in pro-B cells from two patients who are unable to produce Igμ proteins. We find that Igμ expression does not affect VH, D, or JH segment usage and is not required for human Igκ and Igλ recombination or expression. However, the heavy and light chains found in pro-B cells differed from those in peripheral B cells in that they showed unusually long CDR3s. In addition, the Igκ repertoire in Igμ-deficient pro-B cells was skewed to downstream Jκs and upstream Vκs, consistent with persistent secondary V(D)J rearrangements. Thus, Igμ expression is not required for secondary V(D)J recombination in pro-B cells. However, B cell receptor expression shapes the Ab repertoire in humans and is essential for selection against Ab’s with long CDR3s.

Authors

Eric Meffre, Michèle Milili, Carla Blanco-Betancourt, Henedina Antunes, Michel C. Nussenzweig, Claudine Schiff

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Figure 2

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IgH CDR3 characteristics in pro-B cells. (a) VHDJH CDR3 length in 350 pe...
IgH CDR3 characteristics in pro-B cells. (a) VHDJH CDR3 length in 350 peripheral B cell (white bars), 117 in-frame control pro-B (gray bars), and 197 Igμ–/– (black bars) individual sequences. CDR3 length in amino acids (aa) is indicated below. The average CDR3 length for peripheral B, control pro-B, and Igμ–/– pro-B cells was 13.5, 16.5, and 16.0 amino acids, respectively. (b) D reading frame usage in IgH CDR3s from peripheral B, control, and Igμ–/– pro-B cells. The three RF uses reported by Corbett et al. (50) for some commonly used D gene segments are represented. D3-3 and D3-10 encode no intragenic stop codons whereas D6-13, D2-15, D4-17, and D3-22 sequences using RF1 display stop codons.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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