B lymphocytes may escape tolerance by revising their antigen receptors.
B lymphocytes may escape tolerance by revising their antigen receptors.
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DOI：
10.1084/jem.177.4.1165
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发表时间：
1993-04-01
期刊：
影响因子：
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通讯作者：
Weigert M
中科院分区：
文献类型：
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作者：
Radic MZ;Erikson J;Litwin S;Weigert M
为了探索预防非自身免疫小鼠自身反应性的机制，分析了与转基因抗DNA重链相关的内源性免疫球蛋白（IG）轻链（L）。来自这些小鼠的脾B细胞杂交瘤的抗体不结合双链DNA（dsDNA），并且它们的L链序列显示偏向使用V κ和J κ基因片段。本次调查中的44条L链仅由18个生殖系基因编码。六个基因，每个属于一个不同的V κ组，被使用一次以上，占所有序列的四分之三。基于V κ基因的分布，该转基因小鼠品系中的L链库估计为37个V κ基因。最常见的基因，V κ 12/13组的成员，被确定在16个杂种。此外，大多数V κ基因使用J κ 5。我们解释V κ和J κ基因片段的偏斜表示是由阴性选择引起的。基于这些数据，我们认为通过能够编辑自身反应性IG的校正机制，将引起抗dsDNA反应性的V κ重排从库中去除。
To explore mechanisms that prevent autoreactivity in nonautoimmune mice, endogenous immunoglobulin (Ig) light (L) chains that associate with a transgenic anti-DNA heavy chain were analyzed. The antibodies from splenic B cell hybridomas of such mice did not bind double- stranded DNA (dsDNA) and their L chain sequences showed a biased use of V kappa and J kappa gene segments. The 44 L chains in this survey were coded for by just 18 germline genes. Six of the genes, each belonging to a different V kappa group, were used more than once and accounted for three fourths of all sequences. Based on the distribution of V kappa genes, the L chain repertoire in this line of transgenic mice was estimated at 37 V kappa genes. The most frequently observed gene, a member of the V kappa 12/13 group, was identified in 16 hybrids. In addition, the majority of V kappa genes used J kappa 5. We interpret the skewed representation of V kappa and J kappa gene segments to result from negative selection. Based on the data, we suggest that V kappa rearrangements giving rise to anti-dsDNA reactivity are removed from the repertoire by a corrective mechanism capable of editing self- reactive Ig.