The fate of self-reactive B cells depends primarily on the degree of antigen receptor engagement and availability of T cell help.
The fate of self-reactive B cells depends primarily on the degree of antigen receptor engagement and availability of T cell help.
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DOI：
10.1084/jem.183.5.2313
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发表时间：
1996-05-01
期刊：
影响因子：
--
通讯作者：
Basten A
中科院分区：
文献类型：
--
作者：
Fulcher DA;Lyons AB;Korn SL;Cook MC;Koleda C;Parish C;Fazekas de St Groth B;Basten A
与正常B细胞相比，来自共表达鸡蛋溶菌酶(HEL)和重排的抗HEL免疫球蛋白基因的耐受双转基因(DBL-TG)小鼠的自身反应性B细胞的寿命相对较短，无论它们是以多价膜结合形式(mHEL-DBL-TG小鼠)还是以可溶性形式(SHEL-DBL-TG小鼠)暴露于抗原。用细胞内染料5-羧基荧光素二乙酸酯琥珀酰亚胺酯(CFSE)标记抗HEL-Ig-TG脾细胞，并将其注射到非TG受体或多种HEL-TG宿主中，用细胞示踪技术研究了影响这些B细胞与自身抗原相遇后命运的因素。在非甘油三酯受体中，与HEL结合的B细胞持续存在于循环中，并可在脾的滤泡中检测到至少5d。当转移到mHEL-TG或SHEL-TG宿主时，它们被激活，然后在接下来的3d内从血液和脾中迅速消失，与先前报道的短寿命一致。SHEL-TG受者脾的免疫组织化学显示，转移的B细胞已迁移到动脉周围淋巴鞘(PALS)的外缘，在那里可检测到24小时后消失。B细胞在外周PAL中的定位取决于与血清HEL浓度在0.5-15 ng/ml之间的Ig受体结合的临界阈值，但不限于内源性表达的HEL，因为在转移到给予外源(外来)HEL的非TG受体后，观察到相同的迁移模式。此外，骨髓来源的未成熟Ig-TgB细胞归巢于SHEL-Tg小鼠的外周PAL，然后以与成熟B细胞相同的速度消失，这表明成熟阶段并不影响在宽容环境中自我反应性B细胞的命运。另一方面，转移到SHEL-DBL-TG受体中的HEL结合的B细胞在3d的研究期间持续存在，显然是由于抗原的可获得性不足，这一事实表明，被转移的B细胞上Ig受体下调的程度比SHEL-TG受体的受体下调程度要小得多。如果在转移到SHEL-TG受体时，T细胞帮助提供给Ig-TGB细胞，作为B细胞表面主要组织相容性复合肽复合体的预激活的CD4+T细胞，与HEL结合的B细胞通过脾的外部PAL迁移到毛囊，在那里它们形成生发中心，或者迁移到邻近的红髓，在那里它们形成增殖灶并分泌大量的抗HEL抗体。综上所述，这些结果表明，自身抗原和B细胞之间相互作用的结果在很大程度上取决于受体的结合程度和T细胞帮助的可用性。
Self-reactive B cells from tolerant double-transgenic (Dbl-Tg) mice coexpressing hen egg lysozyme (HEL) and rearranged anti-HEL immunoglobulin genes have a relatively short life span when compared to normal B cells, irrespective of whether they are exposed to antigen in multivalent membrane-bound form (mHEL-Dbl-Tg mice) or soluble form (sHEL-Dbl-Tg mice). The factors responsible for determining the fate of these B cells after encounter with self-antigen were investigated using a cell-tracking technique in which anti-HEL Ig-Tg spleen cells were labeled with the intracellular dye 5-carboxyfluorescein diacetate- succinimidyl ester (CFSE) and injected either into non-Tg recipients or a variety of HEL-Tg hosts. In non-Tg recipients, HEL-binding B cells persisted in the circulation and could be detected in the follicles of the spleen for at least 5 d. On transfer into either mHEL-Tg or sHEL-Tg hosts, they underwent activation and then rapidly disappeared from the blood and spleen over the next 3 d, consistent with the short life span reported previously. Immunohistology of spleens from sHEL-Tg recipients indicated that the transferred B cells had migrated to the outer margins of the periarteriolar lymphoid sheath (PALS), where they were detectable for 24 h before being lost. The positioning of B cells in the outer PALS depended on a critical threshold of Ig receptor binding corresponding to a serum HEL concentration between 0.5 and 15 ng/ml, but was not restricted to endogenously expressed HEL in that the same migratory pattern was observed after transfer into non-Tg recipients given exogenous (foreign) HEL. Moreover, bone marrow-derived immature Ig-Tg B cells homed to the outer PALS of sHEL-Tg mice and then disappeared at the same rate as mature B cells, indicating that the stage of maturation did not influence the fate of self-reactive B cells in a tolerant environment. On the other hand, HEL-binding B cells transferred into sHEL-Dbl-Tg recipients persisted over the 3-d period of study, apparently due to insufficient availability of antigen, as indicated by the fact that the degree of Ig receptor downregulation on the transferred B cells was much less than in sHEL-Tg recipients. If T cell help was provided to Ig-Tg B cells at the time of transfer into sHEL-Tg recipients in the form of preactivated CD4+ T cells specific for major histocompatibility complex-peptide complexes on the B cell surface, HEL-binding B cells migrated through the outer PALS of the spleen to the follicle, where they formed germinal centers, or to adjacent red pulp, where they formed proliferative foci and secreted significant amounts of anti-HEL antibody. Taken together, these results indicated that the outcome of the interaction between self-antigen and B cells is largely determined by a combination of the degree of receptor engagement and availability of T cell help.
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影响因子：
56.9
作者：
ADELSTEIN, S;PRITCHARDBRISCOE, H;GOODNOW, CC
通讯作者：
GOODNOW, CC
DOI：
10.1084/jem.179.2.425
发表时间：
1994-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cooke MP;Heath AW;Shokat KM;Zeng Y;Finkelman FD;Linsley PS;Howard M;Goodnow CC
通讯作者：
Goodnow CC
影响因子：
64.5
作者：
HARTLEY, SB;COOKE, MP;GOODNOW, CC
通讯作者：
GOODNOW, CC
影响因子：
2.2
作者：
LYONS, AB;PARISH, CR
通讯作者：
PARISH, CR
对（4-羟基-3-硝基苯基）乙酰基的初级免疫反应的原位研究。二.动脉周围淋巴鞘相关病灶和生发中心的常见克隆起源。
DOI：
10.1084/jem.176.3.679
发表时间：
1992-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jacob J;Kelsoe G
通讯作者：
Kelsoe G