Turner Marian L, Hawkins Edwin D, Hodgkin Philip D
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
J Immunol. 2008 Jul 1;181(1):374-82. doi: 10.4049/jimmunol.181.1.374.
Differentiation to Ab secreting and isotype-switched effector cells is tightly linked to cell division and therefore the degree of proliferation strongly influences the nature of the immune response. The maximum number of divisions reached, termed the population division destiny, is stochastically distributed in the population and is an important parameter in the quantitative outcome of lymphocyte responses. In this study, we further assessed the variables that regulate B cell division destiny in vitro in response to T cell- and TLR-dependent stimuli. Both the concentration and duration of stimulation were able to regulate the average maximum number of divisions undergone for each stimulus. Notably, a maximum division destiny was reached during provision of repeated saturating stimulation, revealing that an intrinsic limit to proliferation exists even under these conditions. This limit was linked directly to division number rather than time of exposure to stimulation and operated independently of the survival regulation of the cells. These results demonstrate that a B cell population's division destiny is regulable by the stimulatory conditions up to an inherent maximum value. Division destiny is a crucial parameter in regulating the extent of B cell responses and thereby also the nature of the immune response mounted.
向分泌抗体和发生同种型转换的效应细胞的分化与细胞分裂紧密相关，因此增殖程度强烈影响免疫反应的性质。达到的最大分裂次数，称为群体分裂命运，在群体中是随机分布的，并且是淋巴细胞反应定量结果中的一个重要参数。在本研究中，我们进一步评估了在体外响应T细胞和TLR依赖性刺激时调节B细胞分裂命运的变量。刺激的浓度和持续时间都能够调节每种刺激所经历的平均最大分裂次数。值得注意的是，在提供重复的饱和刺激期间达到了最大分裂命运，这表明即使在这些条件下也存在增殖的内在限制。这个限制直接与分裂次数相关，而不是与暴露于刺激的时间相关，并且独立于细胞的存活调节而运作。这些结果表明，B细胞群体的分裂命运可由刺激条件调节至固有最大值。分裂命运是调节B细胞反应程度从而也调节所产生的免疫反应性质的关键参数。
