Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, United States of Amercia.
Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA, United States of Amercia.
PLoS Pathog. 2018 Apr 16;14(4):e1006967. doi: 10.1371/journal.ppat.1006967. eCollection 2018 Apr.
Kaposi sarcoma herpesvirus (KSHV/HHV-8) is a B cell tropic human pathogen, which is present in vivo in monotypic immunoglobulin λ (Igλ) light chain but polyclonal B cells. In the current study, we use cell sorting to infect specific B cell lineages from human tonsil specimens in order to examine the immunophenotypic alterations associated with KSHV infection. We describe IL-6 dependent maturation of naïve B lymphocytes in response to KSHV infection and determine that the Igλ monotypic bias of KSHV infection in vivo is due to viral induction of BCR revision. Infection of immunoglobulin κ (Igκ) naïve B cells induces expression of Igλ and isotypic inclusion, with eventual loss of Igκ. We show that this phenotypic shift occurs via re-induction of Rag-mediated V(D)J recombination. These data explain the selective presence of KSHV in Igλ B cells in vivo and provide the first evidence that a human pathogen can manipulate the molecular mechanisms responsible for immunoglobulin diversity.
卡波西肉瘤疱疹病毒（KSHV/HHV-8）是一种嗜 B 细胞的人类病原体，在体内以单型免疫球蛋白 λ（Igλ）轻链但多克隆 B 细胞存在。在本研究中，我们使用细胞分选从人扁桃体标本中感染特定的 B 细胞谱系，以检查与 KSHV 感染相关的免疫表型改变。我们描述了 IL-6 依赖性幼稚 B 淋巴细胞对 KSHV 感染的成熟反应，并确定体内 KSHV 感染的 Igλ单型偏倚是由于病毒诱导的 BCR 修正。免疫球蛋白 κ（Igκ）幼稚 B 细胞的感染诱导 Igλ和同种型包含物的表达，最终导致 Igκ 的丧失。我们表明，这种表型转变是通过重新诱导 Rag 介导的 V(D)J 重组发生的。这些数据解释了 KSHV 在体内 Igλ B 细胞中选择性存在的原因，并提供了第一个证据表明人类病原体可以操纵负责免疫球蛋白多样性的分子机制。
