Naive B lymphocytes undergo homeostatic proliferation in response to B cell deficit
Naive B lymphocytes undergo homeostatic proliferation in response to B cell deficit
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DOI：
10.4049/jimmunol.169.12.6795
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发表时间：
2002-12-15
影响因子：
4.4
通讯作者：
Woodland, RT
中科院分区：
文献类型：
--
作者：
Cabatingan, MS;Schmidt, MR;Woodland, RT
幼稚外周B细胞维持在足够的数量和多样性，以产生针对感染因子的有效免疫应答。然而，正常的细胞更新和Ag激活会不断减少该B细胞库的大小和库。稳态（Ag非依赖性）增殖。响应于B细胞耗竭是补偿这种细胞损失的一种机制。我们已经使用纯化的CFSE标记的B细胞和过继转移模型系统来显示未成熟和成熟的B细胞在多种B细胞缺陷（scid、xid、IL-7（-/-）和亚致死照射）宿主中分裂。稳态B细胞增殖是T细胞非依赖性的，并且通过该机制复制的B细胞保留初始B细胞的抗原表型。在B细胞充足的正常或B细胞重建的免疫缺陷受体中，通过竞争成熟滤泡B细胞的作用，复制显著降低。使用xid小鼠和转录因子敲除，我们发现导致稳态B细胞增殖的激活信号需要布鲁顿酪氨酸激酶;然而，c-Rel，一种布鲁顿酪氨酸激酶诱导的NF-κ B/Rel转录因子，对Ag和有丝分裂原刺激至关重要，是不稳定的，表明这种激活途径的独特性。生存和复制信号也可以分开，因为外周B细胞生存所需的转录因子p50（NF-κ B 1）对于稳态复制来说不是必需的。稳态B细胞增殖提供了一种Ag非依赖性机制，用于维持和扩增选择进入成熟B细胞库的幼稚B细胞。
Naive peripheral B cells are maintained in sufficient numbers and diversity to mount effective immune responses against infectious agents. However, the size and repertoire of this B cell pool is constantly diminished by normal cell turnover and Ag activation. Homeostatic (Ag-independent) proliferation. in response to B cell depletion is one mechanism to compensate for this cell loss. We have used purified CFSE-labeled B cells and an adoptive transfer model system to show that immature and mature B cells divide in a variety of B cell-deficient (scid, xid, IL-7(-/-), and sublethally irradiated) hosts. Homeostatic B cell proliferation is T cell independent, and B cells that have replicated by this mechanism retain the antigenic phenotype of naive B cells. Replication is significantly reduced in B cell-sufficient normal or B cell-reconstituted immunodeficient recipients by the action of competing mature follicular B cells. Using xid mice and transcription factor knockouts, we show that the activation signal(s) that, lead to homeostatic B cell proliferation require Bruton's tyrosine kinase; however, c-Rel, a Bruton's tyrosine kinase-induced NF-kappaB/Rel transcription factor critical for Ag and mitogen stimulation, is dispensable, indicating the uniqueness of this activation pathway. Survival and replication signals can also be separated, because the transcription factor p50 (NF-kappaB1), which is required for the survival of peripheral B cells, is not necessary for homeostatic replication. Homeostatic B cell proliferation provides an Ag-independent mechanism for the maintenance and expansion of naive B cells selected into the mature B cell pool.