Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines
Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines
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DOI：
10.4049/jimmunol.167.4.1909
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发表时间：
2001-08-15
影响因子：
4.4
通讯作者：
Weih, F
中科院分区：
文献类型：
--
作者：
Weih, DS;Yilmaz, ZB;Weih, F
高水平的Rel/NF-kappaB家族成员RelB仅限于胸腺、淋巴结和Peyer’s patch的特定区域。在脾脏，RelB表达于小动脉周围淋巴鞘、生发中心（GCs）和边缘区（MZ）。在这项研究中，我们报道了relB缺陷（relB(-/-)）小鼠，与nfkb1（-/-）相反，但与nfkb2（-/-）小鼠相似，在脾脏中Ag攻击后不能形成GCs和滤泡树突状细胞网络。巨噬细胞和B细胞正常组织MZ及其群体也需要RelB。互惠骨髓移植表明，RelB在抗辐射基质细胞中表达，而不是在骨髓来源的造血细胞中表达，是GCs、滤泡树突状细胞网络和MZ结构正确形成所必需的。然而，MZ B细胞的产生需要造血细胞中的ROB。TNF配体/受体家族成员的表达在relB（-/-）脾细胞中仅发生中度改变。相比之下，归巢趋化因子的表达在relB（-/-）脾脏中强烈降低，趋化因子B淋巴细胞趋化因子的mRNA水平特别低。我们的数据表明，TNF/淋巴素下游基质细胞中p52-RelB异源二聚体的激活是归巢趋化因子的正常表达和脾脏微结构正常发育所必需的。
High levels of the Rel/NF-kappaB family member RelB are restricted to specific regions of thymus, lymph nodes, and Peyer's patches. In spleen, RelB is expressed in periarteriolar lymphatic sheaths, germinal centers (GCs), and the marginal zone (MZ). In this study, we report that RelB-deficient (relB(-/-)) mice, in contrast to nfkb1(-/-), but similar to nfkb2(-/-) mice, are unable to form GCs and follicular dendritic cell networks upon Ag challenge in the spleen. RelB is also required for normal organization of the MZ and its population by macrophages and B cells. Reciprocal bone marrow transfers demonstrate that RelB expression in radiation-resistant stromal cells, but not in bone marrow-derived hemopoietic cells, is required for proper formation of GCs, follicular dendritic cell networks, and MZ structures. However, the generation of MZ B cells requires ROB in hemopoietic cells. Expression of TNF ligand/receptor family members is only moderately altered in relB(-/-) splenocytes. In contrast, expression of homing chemokines is strongly reduced in relB(-/-) spleen with particularly low mRNA levels of the chemokine B lymphocyte chemoattractant. Our data indicate that activation of p52-RelB heterodimers in stromal cells downstream of TNF/lymphotoxin is required for normal expression of homing chemokines and proper development of spleen microarchitecture.