Lane P J, Gray D, Oldfield S, MacLennan I C
Eur J Immunol. 1986 Dec;16(12):1569-75. doi: 10.1002/eji.1830161216.
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 (kappa la) 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 kappa lb thoracic duct lymphocytes from donors immunized previously with the TD carrier. This provides test animals where newly produced virgin B cells only express kappa la but where initially most peripheral B cells are kappa lb. 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.
哺乳动物的骨髓在其一生中会产生大量B细胞。其中大多数寿命较短。本报告的主题是研究新形成的未成熟B细胞在何种程度上可被携带半抗原2,4 - 二硝基苯基的胸腺依赖性（TD）抗原和胸腺非依赖性2型（TI - 2）抗原激活。实验方法采用了不同κ免疫球蛋白轻链同种异型的同基因大鼠之间构建的嵌合体。宿主（κ la）大鼠通过全身照射清除外周B细胞，但通过后肢屏蔽保留B淋巴细胞生成能力。它们的外周B细胞池通过转移来自先前用TD载体免疫的供体的κ lb胸导管淋巴细胞进行重建。这提供了这样的实验动物：新产生的未成熟B细胞仅表达κ la，但最初大多数外周B细胞是κ lb。所测试的TD抗原在免疫后的即刻能够激活未成熟和记忆B细胞。然而，长期抗体产生归因于记忆B细胞克隆的反复激活，而没有进一步招募未成熟B细胞。相比之下，TI - 2抗原诱发的抗体最初几乎完全是由于供体外周B细胞的激活。然而，在TI - 2免疫后的一段时间内，宿主产生的抗体量逐渐增加，相应的反应中供体成分下降，以至于到六周时宿主反应占主导。进行了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细胞区室的重新填充速率进一步研究了这些差异的细胞基础。结果表明，宿主对TI - 2抗原产生抗体的开始与宿主B细胞在脾脏边缘区的出现密切相关，而良好的TD宿主抗2,4 - 二硝基苯基反应先于宿主B细胞在该区室的出现。结合其他涉及边缘区B细胞对TI - 2抗原反应的数据对这些结果进行了讨论。
