Andersson K B, Draves K E, Magaletti D M, Fujioka S, Holmes K L, Law C L, Clark E A
Department of Microbiology, University of Washington, Seattle 98195-7242, USA.
Eur J Immunol. 1996 Dec;26(12):3170-8. doi: 10.1002/eji.1830261250.
CD22 is a B cell-restricted surface molecule which may play an important role in interactions between B cells and other cells and in regulating signals through the B cell receptor (BCR) complex. Here we have examined whether the mouse is a suitable in vivo model for studying CD22 functions. In primary and secondary lymphoid organs of adult mice CD22 is on all mature B cells, including resting IgM+IgD+ B cells, IgG+ HSA(lo) memory B cells, syndecan+ plasma cells and CD5+ B cells, but it is not on immature IgM+IgD- B cells. Biochemical analysis revealed that murine CD22 is associated with the IgM receptor in some, but not all, CD22+ B leukemic and lymphoma cell lines; as with human CD22, murine CD22 is rapidly phosphorylated on tyrosine after ligation of the BCR. In the CD22- murine pro-B cell line, FEMCL, CD22 expression was inducible by treatment with phorbol 12-myristate 13-acetate. A genomic fragment of the cd22b allele containing 1.3 kb 5' of exon 1 was sequenced in order to identify potential DNA regulatory elements in the CD22 promoter region. Consensus sequences for transcription factor binding sites including PU.1, AP-1, AP-2, C/EBP and SP-1 were present, but no classical TATA elements or initiator motifs were evident at relevant positions. The 1.3-kb promoter fragment 5' of exon 1 was sufficient for directing basal promoter activity in B and T cells. There was no significant sequence similarity between the murine and human cd22 gene promoters, although both contain repetitive elements and Sp-1 and AP1 binding sites. Thus, murine CD22 shares a number of features with human CD22 and the mouse provides a suitable model system for elucidating the function of CD22 in vivo.
CD22是一种B细胞限制性表面分子，它可能在B细胞与其他细胞之间的相互作用以及通过B细胞受体（BCR）复合物调节信号方面发挥重要作用。在此，我们研究了小鼠是否是研究CD22功能的合适体内模型。在成年小鼠的初级和次级淋巴器官中，CD22存在于所有成熟B细胞上，包括静止的IgM+IgD+B细胞、IgG+HSA(lo)记忆B细胞、syndecan+浆细胞和CD5+B细胞，但不存在于未成熟的IgM+IgD-B细胞上。生化分析表明，在一些（但不是全部）CD22+B白血病和淋巴瘤细胞系中，鼠源CD22与IgM受体相关联；与人类CD22一样，鼠源CD22在BCR连接后酪氨酸会迅速磷酸化。在CD22-鼠源前B细胞系FEMCL中，用佛波酯12-肉豆蔻酸酯13-乙酸酯处理可诱导CD22表达。对包含外显子1上游1.3 kb的cd22b等位基因的基因组片段进行测序，以鉴定CD22启动子区域潜在的DNA调控元件。存在包括PU.1、AP-1、AP-2、C/EBP和SP-1在内的转录因子结合位点的共有序列，但在相关位置没有明显的经典TATA元件或起始基序。外显子1上游1.3 kb的启动子片段足以指导B细胞和T细胞中的基础启动子活性。尽管鼠源和人源cd22基因启动子都含有重复元件以及Sp-1和AP1结合位点，但它们之间没有明显的序列相似性。因此，鼠源CD22与人类CD22具有许多共同特征，小鼠为阐明CD22在体内的功能提供了合适的模型系统。
