Canonical germinal center B cells may not dominate the memory response to antigenic challenge
Canonical germinal center B cells may not dominate the memory response to antigenic challenge
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DOI：
10.1093/intimm/13.5.643
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发表时间：
2001-05-01
影响因子：
4.4
通讯作者：
Cerny, J
中科院分区：
文献类型：
--
作者：
Lu, YF;Singh, M;Cerny, J
脾和骨髓是全身免疫小鼠产生抗体和记忆应答的主要部位。我们检查了在对半抗原硝基苯基（NP）的抗体应答过程中这两个位点中抗体空斑形成细胞（APFC）的VDJ区段库。单个IgG APFC表达V186.2/V3（J558）基因家族的10个V-H区段中的任一个：186.2，102，23，C1 H4，165.1，CH 10，3，593，3，24.8和671.5，脾和BM中的大多数细胞表达与Tyr 95连接的D区段的V186.2基因。在单次免疫后的P月期间，BM中V186.2（+）APFC累积的体细胞突变是脾APFC的3倍（平均8.5对3突变/V-H）;如体内CD 4（+）淋巴细胞耗竭所示，该过程是Th依赖性的。然而，脾脏和BM中的V186.2（+）APFC都有一个复发性W33 L替代，表明它们共同起源于生发中心。表达其他（类似物）V-H节段的APFC在脾脏和BM中均匀存在，但它们积累很少（如果有的话）突变。V186.2（+）APFC在脾脏和骨髓中均发生了高度突变，它们代表了一种新的和意想不到的克隆型，V/D片段由Gly 95代替Tyr 95连接，W33 L缺失，出现了一个新的共享K58 R替换。表达“类似物”V-H基因的APFC包含类似于20%的回忆应答，并且没有积累更多的突变，但它们的亲和力在记忆V186.2（+）细胞的范围内。这些数据表明，对半抗原的晚期初级和次级反应可能由不同的B细胞谱系产生，并且某些克隆型可能在没有广泛突变和扩增的情况下到达记忆池。
Spleen and bone marrow (BM) are the major sites of antibody production and anamnestic response in systemically immunized mice. We examined the VDJ segment repertoire of antibody plaque-forming cells (APFC) in those two sites in the course of antibody responses to the hapten nitrophenyl (NP), Individual IgG APFC expressed any one of 10 V-H segments of the V186.2/V3 (J558) gene family: 186.2, 102, 23, C1H4, 165.1, CH10, 3, 593,3, 24.8 and 671.5, The majority of cells in both spleen and BM expressed the V186.2 gene joined to a D segment with Tyr95, During a P-month period after a single immunization, the V186.2(+) APFC in BM accumulated 3 times as many somatic mutations than splenic APFC (average 8.5 versus 3 mutations/V-H); this process was Th dependent as shown by in vivo depletion of CD4(+) lymphocytes. However, the V186.2(+) APFC in both spleen and BM shared a recurrent W33L replacement, indicating their common origin from germinal centers. The APFC expressing the other (analogue) V-H segments were evenly represented in the spleen and BM, but they accumulated few, if any, mutations. The anamnestic V186.2(+) APFC were highly mutated both in the spleen and BM; they represented a new and unexpected clonotype, The V/D segments were joined by Gly95 instead of Tyr95, the W33L was absent and a new shared K58R replacement appeared. The APFC expressing the 'analogue' V-H genes comprised similar to 20% of the anamnestic response and did not accumulate more mutations, but their affinities were in the range of the memory V186.2(+) cells. These data suggest that the late primary and secondary responses to a hapten may be born by different B cell lineages, and that some clonotypes may reach the memory pool without an extensive mutation and expansion.