LeMaoult J, Delassus S, Dyall R, Nikolić-Zugić J, Kourilsky P, Weksler M E
Division of Geriatrics and Gerontology, Cornell University Medical College, New York 10021, USA.
J Immunol. 1997 Oct 15;159(8):3866-74.
The effect of age on the diversity of the murine Ig heavy chain repertoire has been studied in unimmunized C57BL/6 mice. We examined the heterogeneity of complementarity-determining region 3 (CDR3) sizes of Ig mRNA of the IgM and IgG isotypes using two VH families, VHJ558 and VHQ52, which together account for approximately 65% of the Ab repertoire. The broad and bell-shaped profiles representing the diversity of the VHJ558 family in the spleen of 2- to 6-mo-old C57BL/6 mice becomes significantly less diverse after 12 mo of age and by 18 mo of age, single CDR3 sizes that dominate the profiles can be observed in the spleens of > 85% of the mice. Readable sequences have been obtained from 40 dominant mRNA CDR3 size species indicating that they represent clonal populations of B lineage. There are no significant homologies among these sequences. Clones of B lymphocytes that express a dominant CDR3 mRNA species can also be found in the bone marrow, the mesenteric lymph nodes, and the thymus of C57BL/6 mice > 18 mo of age. Some clones of B cells can be detected in only one lymphoid compartment; others are found in two or more compartments. The splenic B cell clones in C57BL/6 mice > 18 mo of age are stable for at least 2 mo. The CDR3 mRNA species that dominate the splenic repertoire of Ig mRNA-expressing cells in vivo do not dominate the repertoire of splenic B cells activated in vitro by bacterial LPS, suggesting that they represent a modest population of B cells expressing high levels of Ig mRNA.
在未免疫的C57BL/6小鼠中研究了年龄对鼠Ig重链库多样性的影响。我们使用两个VH家族VHJ558和VHQ52，检测了IgM和IgG同种型的Ig mRNA互补决定区3（CDR3）大小的异质性，这两个家族共同约占抗体库的65%。代表2至6月龄C57BL/6小鼠脾脏中VHJ558家族多样性的宽峰和钟形图谱在12月龄后多样性显著降低，到18月龄时，在超过85%的小鼠脾脏中可观察到主导图谱的单一CDR3大小。已从40种占主导的mRNA CDR3大小种类中获得可读序列，表明它们代表B谱系的克隆群体。这些序列之间没有明显的同源性。在18月龄以上的C57BL/6小鼠的骨髓、肠系膜淋巴结和胸腺中也可发现表达占主导的CDR3 mRNA种类的B淋巴细胞克隆。一些B细胞克隆仅在一个淋巴区室中可检测到；其他的则在两个或更多区室中发现。18月龄以上C57BL/6小鼠脾脏中的B细胞克隆至少稳定2个月。在体内占主导的表达Ig mRNA细胞的脾脏库的CDR3 mRNA种类，在体外由细菌LPS激活的脾脏B细胞库中并不占主导，这表明它们代表表达高水平Ig mRNA的适度B细胞群体。
