ROLE OF ACCESSORY CELLS IN B-CELL ACTIVATION .3. CELLULAR ANALYSIS OF PRIMARY IMMUNE-RESPONSE DEFICITS IN CBA-N MICE - PRESENCE OF AN ACCESSORY CELL-B CELL-INTERACTION DEFECT
ROLE OF ACCESSORY CELLS IN B-CELL ACTIVATION .3. CELLULAR ANALYSIS OF PRIMARY IMMUNE-RESPONSE DEFICITS IN CBA-N MICE - PRESENCE OF AN ACCESSORY CELL-B CELL-INTERACTION DEFECT
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DOI：
10.1084/jem.152.5.1194
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发表时间：
1980-01-01
影响因子：
15.3
通讯作者：
SINGER, A
中科院分区：
文献类型：
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作者：
BOSWELL, HS;NERENBERG, MI;SINGER, A
X连锁CBA/N遗传缺陷对小鼠产生对胸腺依赖性和胸腺非依赖性抗原的初级应答的能力的影响通过比较异常（CBA/N × N）的能力来评估。DBA/2）F1雄性小鼠和正常（D8 A/2 × DBA/2）F1雄性小鼠。CBA/N）F1雄性小鼠产生2，4，6-三硝基苯基（TNP）特异性空斑形成细胞对TNP-匙孔血蓝蛋白（KLH）、TNP-偶联Ficoll（TNP-Ficoll）、TNP-流产布鲁氏菌（BA）和TNP- [沙门氏菌]脂多糖（LPS）的反应。本研究中使用的相互F1组合仅在它们的X染色体的起源上有遗传差异，但在免疫学上有差异（CBA/N × N）。DBA/2）F1雄性小鼠表达所有CBA/N免疫异常，而（DBA/2 ×CBA/N）F1雄性小鼠免疫学正常。对TNP-KLH的胸腺依赖性反应的分析表明，异常F1小鼠能够在体内对高剂量的TNP-KLH产生主要反应;但未能对正常F1小鼠仍具有免疫原性的次优剂量的TNP-KLH产生反应。在有限的体外微量培养条件下，异常F1小鼠未能产生主要的胸腺依赖性反应的任何剂量的TNP-KLH，即使在相同的条件下，正常F1小鼠一贯响应于广泛的抗原剂量范围。通过测定来自这些小鼠的辅助细胞、T细胞和B细胞的纯化群体在对TNP-KLH的应答中发挥功能的能力，研究了异常F1小鼠在体外对TNP-KLH应答失败的细胞基础。异常F1小鼠的辅助T细胞和抗原呈递辅助细胞与正常F1小鼠的等效细胞群一样具有能力和功能。CBA/N小鼠不能产生对TNP-KLH的初级体外应答仅仅是其B细胞群缺陷的结果，使得来自这些小鼠的B细胞不能被感受态辅助T细胞和/或感受态辅助细胞触发。类似地，异常F1小鼠体内或体外对TNP-Ficoll应答的失败不是TNP-Ficoll辅助细胞呈递缺陷的结果，而是来自这些小鼠的B细胞不能被胜任的TNP-Ficoll呈递辅助细胞激活的结果。与来自异常F1小鼠的B细胞在体外对TNP-KLH或TNP-Ficoll的应答中不能被激活相反，来自异常F1小鼠的B细胞被触发对TNP-BA和TNP-LPS（不需要辅助细胞呈递的抗原）应答。来自异常F1小鼠的B细胞在需要辅助细胞抗原呈递的应答中被激活的特异性失败表明，X连锁CBA/N遗传缺陷导致B细胞群体可能缺乏与抗原呈递辅助细胞相互作用的能力。用TNP-BA（一种来自异常F1小鼠的B细胞对其有反应的抗原）脉冲辅助细胞，并将其作为TNP-BA呈递细胞加入培养物中。尽管来自异常F1小鼠的B细胞被触发并响应于悬浮液中的游离TNP-BA，但相同的异常B细胞群不能被脉冲辅助细胞呈递的TNP-BA触发。显然，异常CBA/N小鼠所拥有的B细胞群不能通过它们与抗原呈递辅助细胞的相互作用而被触发，而不管所呈递的抗原是什么。CBA/N小鼠中观察到的许多免疫异常可能是抗原呈递辅助细胞和CBA/N B细胞之间单一相互作用缺陷的结果。
The effect of the X-linked CBA/N genetic defect on the ability of mice to generate primary responses to thymic-dependent and thymic-independent antigens was assessed by comparing the ability of abnormal (CBA/N .times. DBA/2)F1 male mice and normal (D8A/2 .times. CBA/N)F1 male mice to generate 2,4,6-trinitrophenyl (TNP)-specific plaque-forming cell responses to TNP-keyhole limpet hemocyanin (KLH), TNP-conjugated Ficoll (TNP-Ficoll), TNP-Brucella abortus (BA), and TNP- [Salmonella minnesota] lipopolysaccharide (LPS). The reciprocal F1 combinations used in this study differ genetically only in the origin of their X chromosome, but differ immunologically in that (CBA/N .times. DBA/2)F1 male mice express all the CBA/N immune abnormalities, whereas (DBA/2 .times. CBA/N)F1 male mice are immunologically normal. Analysis of thymic-dependent responses to TNP-KLH revealed that abnormal F1 mice were capable of generating primary responses in vivo to high doses of TNP-KLH; but failed to generate responses to suboptimal doses of TNP-KLH that were still immunogenic for normal F1 mice. Under limiting in vitro microculture conditions, the abnormal F1 mice failed to generate primary thymic-dependent responses to any dose of TNP-KLH, even though under the identical conditions normal F1 mice consistently responded to a wide antigen dose range. The cellular basis of the failure of abnormal F1 mice to respond in vitro to TNP-KLH was investigated by assaying the ability of purified populations of accessory cells, T cells, and B cells from these mice to function in responses to TNP-KLH. Helper T cells and antigen-presenting accessory cells from abnormal F1 mice were competent and functioned as well as the equivalent cell populations from normal F1 mice. The failure of CBA/N mice to generate primary in vitro responses to TNP-KLH was solely the result of a defect in their B cell population such that B cells from these mice failed to be triggered by competent helper T cells and/or competent accessory cells. Similarly, the failure of abnormal F1 mice to respond either in vivo or in vitro to TNP-Ficoll was not the result of defective accessory cell presentation of TNP-Ficoll, but was the result of the failure of B cells from these mice to be activated by competent TNP-Ficoll-presenting accessory cells. In contrast to the failure of B cells from abnormal F1 mice to be activated in vitro in response to either TNP-KLH or TNP-Ficoll, B cells from abnormal F1 mice were triggered to respond to TNP-BA and TNP-LPS, antigens that did not require accessory cell presentation. The specific failure of B cells from abnormal F1 mice to be activated in repsonses that required antigen-presentation by accessory cells suggested the possibility that the X-linked CBA/N genetic defect resulted in B cell populations that might be deficient in their ability to interact with antigen-presenting accessory cells. Accessory cells were pulsed with TNP-BA (an antigen to which B cells from abnormal F1 mice responded) and added to culture as TNP-BA-presenting cells. Although B cells from abnormal F1 mice were triggered and responded to TNP-BA free in suspension, the same abnormal B cell populations failed to be triggered by TNP-BA presented by pulsed accessory cells. Apparently, the B cell populations that abnormal CBA/N mice possess fail to be triggered by their interaction with antigen-presenting accessory cells, regardless of the antigen being presented. Many of the immune abnormalities observed in CBA/N mice may be the result of a single interaction defect between antigen-presenting accessory cells and CBA/N B cells.