免疫球蛋白是球蛋白家族中的一員，是免疫系統中的淋巴球用于攻擊外來物并保護人體的一種抗體分子，然而，與其他基因相比，負責編碼免疫球蛋白的免疫球蛋白基因（Ig）更容易頻繁發生變異，為什么呢？如今，研究人員們發現一些線索，可以解釋Ig頻繁發生變異的原因，新成果發表在12月在線出版的《自然—免疫學》期刊上。

在一種活化誘導胞啶核苷脫氨酶（AID）的引導下，Ig基因被一種程序化變異過程高度多樣化。盡管AID總是優先傾向于靶向Ig，其他基因也能被AID異化，而且，AID所引導的異化還會導致B細胞淋巴瘤和其他惡性腫瘤的發展。

為了查明AID征募的機制，Rafael Casellas和Michel Nussenzweig合作，聯合繪制了遍及全基因組的AID結合位點圖。令人吃驚的是，AID的結合位點雜亂無章，比如，在與轉錄活性基因上的靜態RNA聚合酶復合體相關的位點上，它與數千非Ig均有接合，這可以解釋AID調控變異的脫靶標現象。Ig也會特別征集其他因子如RPA形成復合體，這種復合體與Ig頻繁發生的變化有關。

Deep-sequencing identification of the genomic targets of the cytidine deaminase AID and its cofactor RPA in B lymphocytes

Arito Yamane,Wolfgang Resch,Nan Kuo,Stefan Kuchen,Zhiyu Li,Hong-wei Sun,Davide F Robbiani,Kevin McBride,Michel C Nussenzweig& Rafael Casellas

The cytidine deaminase AID hypermutates immunoglobulin genes but can also target oncogenes, leading to tumorigenesis. The extent of AID's promiscuity and its predilection for immunoglobulin genes are unknown. We report here that AID interacted broadly with promoter-proximal sequences associated with stalled polymerases and chromatin-activating marks. In contrast, genomic occupancy of replication protein A （RPA）, an AID cofactor, was restricted to immunoglobulin genes. The recruitment of RPA to the immunoglobulin loci was facilitated by phosphorylation of AID at Ser38 and Thr140. We propose that stalled polymerases recruit AID, thereby resulting in low frequencies of hypermutation across the B cell genome. Efficient hypermutation and switch recombination required AID phosphorylation and correlated with recruitment of RPA. Our findings provide a rationale for the oncogenic role of AID in B cell malignancy.