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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 3

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Igκ light chain repertoire in pro-B cells. (a) Jκ usage in 108 periphera...
Igκ light chain repertoire in pro-B cells. (a) Jκ usage in 108 peripheral B, 22 control pro-B, 38 Igμ–/–, and 37 IgμΔ pro-B VκJκ individual sequences. Percentages of Jκ usage are indicated. (b) Vκ usage in upstream Jκ1 and Jκ2 (Jκ1-2; top) and downstream Jκ3, Jκ4, and Jκ5 (Jκ3-4-5; bottom) rearrangements of peripheral B cells (white bars), control pro-B (light gray bars), Igμ–/– (black bars), and IgμΔ (darkgray bars) pro-B cells. The Vκ genes are subdivided in four groups on the locus (84). The percentages of each Vκ group are indicated on the y axis. *Statistically significant difference (P < 0.001).

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

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Referenced in 8 patents
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