Differences in the recruitment of virgin B cells into antibody responses to thymus‐dependent and thymus‐independent type‐2 antigens
Differences in the recruitment of virgin B cells into antibody responses to thymus‐dependent and thymus‐independent type‐2 antigens
复制标题
原始 B 细胞募集到胸腺依赖性和胸腺非依赖性 2 型抗原的抗体反应中的差异
DOI：
10.1002/eji.1830161216
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发表时间：
1986
影响因子：
5.4
通讯作者：
I. Maclennan
中科院分区：
文献类型：
--
作者：
P. Lane;D. Gray;S. Oldfield;I. Maclennan
哺乳动物的骨髓在一生中都会产生大量的 B 细胞。其中大多数的寿命很短。本报告的主题是研究携带半抗原 2,4-二硝基苯基的胸腺依赖性 (TD) 和胸腺非依赖性 2 型 (TI-2) 抗原可在多大程度上激活新形成的原始 B 细胞。该实验方法使用不同κ免疫球蛋白轻链同种异型的同源大鼠之间产生的嵌合体。宿主(xla)大鼠通过全身照射耗尽了外周B细胞，但通过屏蔽后肢保留了B淋巴细胞生成能力。他们的外周B细胞池是通过从先前用TD载体免疫的供体转移xlb胸导管淋巴细胞来重建的。这提供了测试动物，其中新产生的原始B细胞仅表达xla，但最初大多数外周B细胞表达xlb。测试的 TD 抗原能够在免疫后立即激活原始 B 细胞和记忆 B 细胞。然而，长期抗体产生归因于记忆 B 细胞克隆的重复激活，而没有进一步招募原始 B 细胞。相比之下，TI-2 抗原最初引发的抗体几乎完全是由于供体外周 B 细胞的激活而产生的。然而，在 TI-2 免疫后的一段时间内，产生的宿主抗体的数量逐渐增加，而反应的供体成分相应下降，因此六周时宿主反应占主导地位。进行对照实验以表明这些效应不能用同种异型或同种型定向抑制来解释。通过研究新形成的宿主和成熟供体 B 细胞在这些嵌合体中不同 B 细胞区室的再增殖率，进一步研究了这些差异的细胞基础。结果表明，针对 TI-2 抗原的宿主抗体产生的开始与脾边缘区域中宿主 B 细胞的出现密切相关，而良好的 TD 宿主抗 2,4-二硝基苯基反应早于该区室中宿主 B 细胞的出现。这些结果与其他涉及边缘区 B 细胞对 TI-2 抗原反应的数据进行了讨论。
The bone marrow of mammals generate large numbers of B cells throughout life. Most of these have a short life span. The subject of this report is to investigate the extent to which newly formed virgin B cells can be activated by thymus‐dependent (TD) and thymus‐independent type 2 (TI‐2) antigens carrying the hapten 2,4‐dinitrophenyl. The experimental approach used chimeras made between congenic rats of different kappa immunoglobulin light chain allotype. Host (xla) rats were depleted of peripheral B cells by whole body irradiation but had B lymphopoietic capacity conserved by shielding the hind limbs. Their peripheral B cell pool was reconstituted by transfer of xlb thoracic duct lymphocytes from donors immunized previously with the TD carrier. This provides test animals where newly produced virgin B cells only express xla but where initially most peripheral B cells are xlb. The TD antigen tested was able to activated both virgin and memory B cells in the period immediately following immunization. However, long‐term antibody production was attributable to repeated activation of memory B cell clones without further virgin B cell recruitment. By contrast, antibody evoked by the TI‐2 antigen initially was almost exclusively due to activation of donor peripheral B cells. However, over a period following TI‐2 immunization there was a progressive increase in the amount of host antibody produced with corresponding decline of the donor component of the response so that the host response was dominant by six weeks. Control experiments were conducted to show that these effects could not be explained by allotype or isotype‐directed suppression. The cellular basis of these differences was investigated further by studying the rate of repopulation of different B cell compartments in these chimeras by newly formed host and mature donor B cells. The results indicate that the onset of host antibody production to the TI‐2 antigen closely correlated with the appearance of host B cells in the marginal zones of the spleen, whereas good TD host anti‐2,4‐dinitrophenyl responses antedated the appearance of host B cells in this compartment. These results are discussed in relation to other data implicating marginal zone B cells in responses to TI‐2 antigens.