Circulating human B cells that express surrogate light chains display a unique antibody repertoire

Circulating human B cells that express surrogate light chains display a unique antibody repertoire
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DOI:
10.4049/jimmunol.167.4.2151
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发表时间:
2001-08-15
影响因子:
4.4
通讯作者:
Nussenzweig, MC
Nussenzweig, MC
中科院分区:
医学2区
文献类型:
--
作者:
Meffre, E;Chiorazzi, M;Nussenzweig, MC

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共同表达V-preB和传统L链的循环人B细胞(V-preB(+)L(+) B细胞)是最近描述的表达具有自我反应性的抗体的B细胞亚群。对V- preb (+)L(+) B细胞的初步分析仅限于Ig-kappa和小的、未充分利用的V(H)5家族。为了确定通常由V- preb (+)L(+) B细胞表达的抗体是否具有相似的特征,我们分析了三个高表达V-H家族的Ig H链,V(H)1, V(H)3, V(H)4和Ig-lambda。我们发现V- preb (+)L(+) B细胞表达的V(H)1和V(H)3抗体类似于V(H)5,它们表现出增加的J(H)6使用,较长的CDR3s,以及增加的D-D融合频率。所有这三个V-H家族的抗体也显示出倾斜的D阅读框使用,导致疏水氨基酸的优势,这在传统的B细胞中是反选择的。与Ig-kappa基因一样,V-preB(+)L(+) B细胞中的Ig-kappa基因也显示出较长的CDR3s,但它们与Ig-kappa基因的不同之处在于,它们没有显示出受体编辑的证据。我们得出结论,V-preB(+)L(+) B细胞表达的大量H链和L链抗体显示出与自反应性抗体相关的特征。
Circulating human B cells that coexpress V-preB and conventional L chains (V-preB(+)L(+) B cells) are a recently described subset of B cells that express Abs with features of self-reactivity. Initial analysis of V-preB(+)L(+) B cells was limited to Ig-kappa and to the small, underused V(H)5 family. To determine whether Abs commonly expressed by V-preB(+)L(+) B cells show similar features, we analyzed Ig H chains from three highly expressed V-H families, V(H)1, V(H)3, and V(H)4, and Ig-lambda. We find that V(H)1 and V(H)3 Abs expressed by V-preB(+)L(+) B cells resemble V(H)5 in that they display increased J(H)6 use, long CDR3s, and an increased frequency of D-D fusions. Abs in all three of these V-H families also show skewed D reading frame use resulting in predominance of hydrophobic amino acids, which are counterselected in conventional B cells. Like Ig-kappa genes, the Ig-kappa genes in V-preB(+)L(+) B cells show long CDR3s, but they differ from Ig-kappa genes in that they display no evidence of receptor editing. We conclude that a large number of H and L chain Abs expressed by V-preB(+)L(+) B cells display features associated with self-reactive Abs.