Madoff L C, Michel J L, Gong E W, Kling D E, Kasper D L
Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4131-6. doi: 10.1073/pnas.93.9.4131.
Group B streptococci (GBS) are the most common cause of neonatal sepsis, pneumonia, and meningitis. The alpha C protein is a surface-associated antigen; the gene (bca) for this protein contains a series of tandem repeats (each encoding 82 aa) that are identical at the nucleotide level and express a protective epitope. We previously reported that GBS isolates from two of 14 human maternal and neonatal pairs differed in the number of repeats contained in their alpha C protein; in both pairs, the alpha C protein of the neonatal isolate was smaller in molecular size. We now demonstrate by PCR that the neonatal isolates contain fewer tandem repeats. Maternal isolates were susceptible to opsonophagocytic killing in the presence of alpha C protein-specific antiserum, whereas the discrepant neonatal isolates proliferated. An animal model was developed to further study this phenomenon. Adult mice passively immunized with antiserum to the alpha C protein were challenged with an alpha C protein-expressing strain of GBS. Splenic isolates of GBS from these mice showed a high frequency of mutation in bca--most commonly a decrease in repeat number. Isolates from non-immune mice were not altered. Spontaneous deletions in the repeat region were observed at a much lower frequency (6 x 10(-4)); thus, deletions in that region are selected for under specific antibody pressure and appear to lower the organism's susceptibility to killing by antibody specific to the alpha C protein. This mechanism of antigenic variation may provide a means whereby GBS evade host immunity.
B族链球菌（GBS）是新生儿败血症、肺炎和脑膜炎的最常见病因。αC蛋白是一种表面相关抗原；该蛋白的基因（bca）包含一系列串联重复序列（每个编码82个氨基酸），这些重复序列在核苷酸水平上是相同的，并表达一个保护性表位。我们先前报道，在14对人类母婴中，有两对的GBS分离株其αC蛋白所含的重复序列数量不同；在这两对中，新生儿分离株的αC蛋白分子大小较小。我们现在通过PCR证明，新生儿分离株包含较少的串联重复序列。在存在αC蛋白特异性抗血清的情况下，母体分离株易被调理吞噬杀伤，而有差异的新生儿分离株则增殖。建立了一个动物模型来进一步研究这一现象。用αC蛋白抗血清被动免疫的成年小鼠，用表达αC蛋白的GBS菌株进行攻击。从这些小鼠分离得到的GBS脾脏分离株显示bca有高频率的突变——最常见的是重复序列数量减少。来自未免疫小鼠的分离株没有改变。在重复区域观察到自发缺失的频率要低得多（6×10^(-4)）；因此，在特定抗体压力下选择该区域的缺失，这似乎降低了该生物体对αC蛋白特异性抗体杀伤的敏感性。这种抗原变异机制可能为GBS逃避宿主免疫提供一种手段。
