Fas is required for clonal selection in germinal centers and the subsequent establishment of the memory B cell repertoire

Fas is required for clonal selection in germinal centers and the subsequent establishment of the memory B cell repertoire
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DOI:
10.1016/s1074-7613(01)00100-5
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发表时间:
2001-02-01
期刊:
影响因子:
32.4
通讯作者:
Takemori, T
Takemori, T
中科院分区:
医学1区
文献类型:
--
作者:
Takahashi, Y;Ohta, H;Takemori, T

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在T细胞依赖性免疫应答中,高亲和力的B细胞被选择并分化为记忆细胞;然而,这一过程背后的机制在很大程度上仍然未知。在这里,我们报告说,选择高亲和力B细胞内的生发中心(GC)是受损的Fas缺陷型Ipr小鼠的主要反应,可能是由于无效的负选择。对照小鼠的记忆区室主要由早期GC产生的前体建立,而Ipr缺陷通过增加晚期GC新产生的前体的募集来扩大记忆区室,导致高度突变的记忆B细胞以高频率积累。这些结果表明,Fas是必需的GC内的克隆选择和记忆B细胞库的建立。
In T cell-dependent immune responses, high-affinity B cells are selected and differentiate into memory cells; however, the mechanism behind this process remains largely unknown. Here, we report that the selection of high-affinity B cells within germinal centers (GCs) is impaired in Fas-deficient Ipr mice in the primary response, probably owing to inefficient negative selection. The memory compartment in control mice is mostly established by precursors generated from the early GCs, whereas the Ipr defect expands the memory compartment by the increased recruitment of newly generated precursors from the late GCs, resulting in the accumulation of heavily mutated memory B cells at high frequency. These results suggest that Fas is required for clonal selection within GCs and the establishment of the memory B cell repertoire.