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Characterization of the expression and gene promoter of CD22 in murine B cells
K B Andersson1, K E Draves, D M Magaletti
1Department of Microbiology, University of Washington, Seattle 98195-7242, USA.
Insights
Mice are a suitable model for studying CD22 functions, a B cell molecule crucial for cell interactions and B cell receptor signaling. Murine CD22 shares key features with human CD22, supporting its use in in vivo research.
Area of Science:
- Immunology
- Molecular Biology
Background:
- CD22 is a B cell-specific surface molecule involved in B cell receptor (BCR) signaling and intercellular interactions.
- Understanding CD22 function is critical for B cell biology and immunology.
Purpose of the Study:
- To evaluate the suitability of the mouse as an in vivo model for studying CD22 functions.
- To characterize the expression and regulation of murine CD22.
Main Methods:
- Analysis of CD22 expression in adult mouse lymphoid organs.
- Biochemical analysis of CD22 association with the BCR complex.
- Induction of CD22 expression in a murine pro-B cell line.
- Sequencing and analysis of the murine CD22 gene promoter region.
Main Results:
- CD22 is expressed on mature B cells in mice but not immature B cells.
- Murine CD22 is phosphorylated upon BCR ligation and associated with the IgM receptor in some cell lines.
- The murine CD22 promoter contains transcription factor binding sites and directs basal promoter activity.
- Murine and human CD22 gene promoters show distinct sequences but share some regulatory elements.
Conclusions:
- The mouse is a suitable in vivo model for investigating CD22 functions.
- Murine CD22 exhibits functional and regulatory similarities to human CD22.
- Further research in mice can elucidate CD22's role in B cell biology.
Abstract:
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.