In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 25 ( 2014-06-24)
Abstract:
Antibody repertoires are known to be shaped by selection for antigen binding. Unexpectedly, we now show that selection also acts on a non–antigen-binding antibody region: the heavy-chain variable (V H )–encoded “elbow” between variable and constant domains. By sequencing 2.8 million recombined heavy-chain genes from immature and mature B-cell subsets in mice, we demonstrate a striking gradient in V H gene use as pre-B cells mature into follicular and then into marginal zone B cells. Cells whose antibodies use V H genes that encode a more flexible elbow are more likely to mature. This effect is distinct from, and exceeds in magnitude, previously described maturation-associated changes in heavy-chain complementarity determining region 3, a key antigen-binding region, which arise from junctional diversity rather than differential V H gene use. Thus, deep sequencing reveals a previously unidentified mode of B-cell selection.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1403278111
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2014
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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