DeFranco A L, Kung J T, Paul W E
Immunol Rev. 1982;64:161-82. doi: 10.1111/j.1600-065x.1982.tb00423.x.
The activation of B lymphocyte subpopulations by anti-immunoglobulin and by LPS has been examined. All resting B cells were stimulated to grow larger (i.e. to go from G0 phase to mid G1 phase of the cell cycle) by the continuous presence of anti-mu antibodies. A subpopulation oif these B cells, 30-50% in normal mouse strains, entered S phase in response to large doses of anti-mu. This subpopulation, probably Lyb5+, was completely absent in mice with the xid-determined immune defect. Another, apparently distinct subpopulation, comprising about 25% of the cells, and probably present in xid mice, was sensitive to a proliferative signal delivered by LPS, if the cells had first been cultured for 24 h in the presence of a dose of anti-mu that was sufficient to cause cell enlargement. The fraction of B cells responding to LPS in this way was significantly larger than the fraction responding to LPS alone, suggesting that anti-mu is superior to LPS at inducing the G0 to G1 transition. Based on these results we propose a model of the control of B cell growth and proliferation. Anti-Ig antibodies, or epitopes on conventional antigens, combine with and cross-link B cell receptors, causing the cells to enter G1 and to develop sensitivity to late G1 stimuli, which determine whether they will then enter S phase. These stimuli are provided either by a high dose of anti-mu or by LPS. These agents may work directly or may stimulate other cells to produce B cell Growth Factor (BCGF) and/or related regulatory molecules which may be the actual late G1 stimuli. Distinct B cell types are sensitive to distinct mechanisms for control of proliferation. A new monoclonal antibody, 14G8, which recognizes only a fraction of B cells (30% in normal mice and about 65% in xid mice), was used to separate B cell subpopulations based on the presence or absence of the cell surface antigen recognized by this antibody. The results suggest that 14G8 expression is negatively correlated with Lyb5 expression, although not absolutely. Indeed 14G8+ B cells respond quite well to anti-mu (32% the cells enter S phase). Since Lyb5- B cells are believed not to proliferate in response to anti-mu, this would suggest that a sizeable fraction of the 14G8+ B cells are also Lyb5+. The 14G8+ and 14G8- B cell subpopulations were found to be functionally distinct in that the former responded very well to LPS, whereas the latter responded very poorly. Models of B cell development based on expression of these membrane antigens are presented.
已经研究了抗免疫球蛋白和脂多糖（LPS）对B淋巴细胞亚群的激活作用。通过持续存在抗μ抗体，所有静止的B细胞都被刺激生长得更大（即从细胞周期的G0期进入G1期中期）。在正常小鼠品系中，这些B细胞的一个亚群（占30 - 50%）在大剂量抗μ抗体作用下进入S期。这个亚群可能是Lyb5阳性，在具有xid基因决定的免疫缺陷的小鼠中完全不存在。另一个明显不同的亚群，约占细胞总数的25%，可能存在于xid小鼠中，如果细胞首先在足以引起细胞增大的一定剂量抗μ抗体存在下培养24小时，它对LPS传递的增殖信号敏感。以这种方式对LPS作出反应的B细胞比例明显大于仅对LPS作出反应的比例，这表明抗μ在诱导从G0期到G1期的转变方面优于LPS。基于这些结果，我们提出了一个B细胞生长和增殖控制的模型。抗Ig抗体或常规抗原上的表位与B细胞受体结合并使其交联，导致细胞进入G1期并对G1期后期刺激产生敏感性，这些刺激决定它们随后是否进入S期。这些刺激由高剂量抗μ抗体或LPS提供。这些因子可能直接起作用，也可能刺激其他细胞产生B细胞生长因子（BCGF）和/或相关调节分子，这些分子可能是实际的G1期后期刺激物。不同的B细胞类型对不同的增殖控制机制敏感。一种新的单克隆抗体14G8，它只识别一部分B细胞（正常小鼠中占30%，xid小鼠中约占65%），被用于根据是否存在该抗体识别的细胞表面抗原分离B细胞亚群。结果表明，14G8的表达与Lyb5的表达呈负相关，尽管不是绝对的。实际上，14G8阳性B细胞对抗μ抗体反应良好（32%的细胞进入S期）。由于据信Lyb5阴性B细胞对抗μ抗体不增殖，这表明相当一部分14G8阳性B细胞也是Lyb5阳性。发现14G8阳性和14G8阴性B细胞亚群在功能上是不同的，前者对LPS反应良好，而后者反应很差。文中还给出了基于这些膜抗原表达的B细胞发育模型。
