Taking advantage: high-affinity B cells in the germinal center have lower death rates, but similar rates of division, compared to low-affinity cells.

Taking advantage: high-affinity B cells in the germinal center have lower death rates, but similar rates of division, compared to low-affinity cells.
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DOI:
10.4049/jimmunol.0902452
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发表时间:
2009-12-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Shlomchik MJ
Shlomchik MJ
中科院分区:
其他
文献类型:
--
作者:
Anderson SM;Khalil A;Uduman M;Hershberg U;Louzoun Y;Haberman AM;Kleinstein SH;Shlomchik MJ

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产生高亲和力抗体(Abs)的B淋巴细胞对于保护免受细胞外病原体如细菌和寄生虫的侵害是至关重要的。在免疫应答期间选择高亲和力B细胞的过程从未被阐明。虽然已经表明,高亲和力细胞直接胜过低亲和力细胞在生发中心(GC)2,是否也有这些细胞之间的内在差异还没有解决。可能是高亲和力细胞增殖更快或更可能进入细胞周期,从而超过低亲和力细胞。或者,更高亲和力的细胞可能对生发中心的细胞死亡具有相对更强的抵抗力。通过比较对相同抗原的高亲和力和低亲和力B细胞,我们在此表明,即使在没有竞争的情况下,低亲和力细胞也比高亲和力细胞具有内在更高的死亡率。这表明GC反应中的选择至少部分是由于控制了高亲和力B细胞的存活,而不是由于与低亲和力B细胞相比赋予这些细胞的增殖优势。控制GC中低亲和力和高亲和力B细胞的存活而不是增殖,不仅在初级反应中而且在记忆反应中允许更大的多样性。
B lymphocytes producing high affinity antibodies (Abs) are critical for protection from extracellular pathogens, such as bacteria and parasites. The process by which high affinity B cells are selected during the immune response has never been elucidated. Though it has been shown that high affinity cells directly outcompete low affinity cells in the germinal center (GC)2, whether there are also intrinsic differences between these cells has not been addressed. It could be that higher affinity cells proliferate more rapidly or are more likely to enter cell cycle, thereby outgrowing lower affinity cells. Alternatively, higher affinity cells could be relatively more resistant to cell death in the germinal center. By comparing high and low affinity B cells for the same antigen, we show here that low affinity cells have an intrinsically higher death rate than cells of higher affinity, even in the absence of competition. This suggests that selection in the GC reaction is due at least in part to the control of survival of higher affinity B cells and not by a proliferative advantage conferred upon these cells compared to lower affinity B cells. Control over survival rather than proliferation of low and high affinity B cells in the GC allows greater diversity not only in the primary response but also in the memory response.
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