Bennett Jeffrey L, Haubold Kurt, Ritchie Alanna M, Edwards Sydni J, Burgoon Mark, Shearer Andrew J, Gilden Donald H, Owens Gregory P
Department of Neurology, University of Colorado Health Sciences Center, Denver, CO, United States.
J Neuroimmunol. 2008 Aug 13;199(1-2):126-32. doi: 10.1016/j.jneuroim.2008.04.031. Epub 2008 Jun 10.
Using FACS and single cell reverse transcriptase polymerase chain reaction, we examined the cerebrospinal fluid (CSF) IgG VH repertoires from 10 subjects with a clinically isolated demyelinating syndrome (CIS). B and plasma cell repertoires from individual subjects showed similar VH family germline usage, nearly identical levels of post-germinal center somatic hypermutation, and significant overlap in their clonal populations. Repertoires from 7 of 10 CIS subjects demonstrated a biased usage of VH4 and/or VH2 family gene segments in their plasma or B cell repertoires. V-regionbias, however, was not observed in the corresponding peripheral blood CD19+ B cell repertoires from 2 CIS subjects or in normal healthy adults. Clinically, subjects with VH4 or VH2 CSF IgG repertoire bias rapidly progressed to definite MS, whereas individuals without repertoire bias did not develop MS after a minimum of 2 years of follow-up (p=0.01).
我们使用荧光激活细胞分选技术（FACS）和单细胞逆转录聚合酶链反应，检测了10例临床孤立性脱髓鞘综合征（CIS）患者的脑脊液（CSF）IgG VH基因库。个体受试者的B细胞和浆细胞基因库显示出相似的VH家族种系使用情况、几乎相同的生发中心后体细胞超突变水平，以及其克隆群体的显著重叠。10例CIS受试者中有7例的基因库在其浆细胞或B细胞基因库中表现出VH4和/或VH2家族基因片段的偏向性使用。然而，在2例CIS受试者或正常健康成年人的相应外周血CD19+B细胞基因库中未观察到V区偏向性。临床上，具有VH4或VH2脑脊液IgG基因库偏向性的受试者迅速进展为明确的多发性硬化症（MS），而没有基因库偏向性的个体在至少2年的随访后未发展为MS（p=0.01）。
