Lentz V M, Hayes C E, Cancro M P
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
J Immunol. 1998 Apr 15;160(8):3743-7.
Peripheral B cells are divided into two subpopulations, B-1 and B-2, the relationship of which remains obscure. We recently showed that the Bcmd mutation in A/WySnJ mice reduces average B cell life span, yielding 90% fewer peripheral B cells. Despite this defect, A/WySnJ mice have an elevated proportion of peritoneal CD5+ B cells, suggesting that Bcmd may be the first B-cell-intrinsic gene to differentially affect the B-1 and B-2 subpopulations. To test this hypothesis in detail, we have used in vivo BrdU labeling and four-color cytofluorometry to examine the numbers and turnover rates of sIgM+CD23-CD43+ (B-1) and sIgM+CD23+CD43- (B-2) splenocytes in A/WySnJ and A/J mice. The results show the expected 90% reduction of splenic B-2 cells among A/WySnJ mice, but a normal splenic B-1 cell pool. Increased B-1 cell renewal cannot explain this undiminished pool, because BrdU labeling kinetics reveals an identical splenic B-1 subset turnover rate of approximately 4%/day in both A/WySnJ and A/J strains. Thus, B-1 cells are Bcmd-independent but B-2 cells are Bcmd-dependent, suggesting Bcmd functions in a positive signaling pathway that imparts longevity to quiescent B cells, but that is not required for cycling B cells. Moreover these results show that the requisites for maturation and longevity differ between the B-1 and B-2 subsets.
外周B细胞可分为两个亚群，即B-1和B-2，二者之间的关系仍不清楚。我们最近发现，A/WySnJ小鼠中的Bcmd突变会缩短B细胞的平均寿命，导致外周B细胞数量减少90%。尽管存在这一缺陷，A/WySnJ小鼠腹膜CD5+B细胞的比例却有所升高，这表明Bcmd可能是第一个对B-1和B-2亚群产生不同影响的B细胞内在基因。为了详细验证这一假设，我们采用体内BrdU标记和四色细胞荧光分析法，检测了A/WySnJ和A/J小鼠脾脏中sIgM+CD23-CD43+（B-1）和sIgM+CD23+CD43-（B-2）脾细胞的数量和更新率。结果显示，A/WySnJ小鼠脾脏中的B-2细胞数量如预期般减少了90%，但B-1细胞池正常。B-1细胞更新增加并不能解释这一未减少的细胞池，因为BrdU标记动力学显示，A/WySnJ和A/J品系中脾脏B-1亚群的更新率相同，约为每天4%。因此，B-1细胞不依赖Bcmd，而B-2细胞依赖Bcmd，这表明Bcmd在一个正向信号通路中发挥作用，该通路赋予静止B细胞长寿特性，但对循环B细胞并非必需。此外，这些结果表明，B-1和B-2亚群在成熟和长寿方面的要求不同。
